Document Sample
					    Effect of Glucocorticoids and Limiting Nursing on the
 Carbohydrate Digestive Capacity and Growth Rate of Piglets
    Richard P. Chapple, Jose A. Cuaron and Robert A. Easter

                   J ANIM SCI 1989, 67:2956-2973.

The online version of this article, along with updated information and
          services, is located on the World Wide Web at:


              Downloaded from by guest on December 22, 2011
                   AND GROWTH RATE OF PIGLETS
                Richard P. Chapple 1, Jose A. Cuaron2 and Robert A. Easter3

                                   University of Illinois4, Urbana 61801

      The influence of glucocorticoid administration and limited nursing on piglet
   carbohydrase enzyme development and subsequent growth was examined in three
   experiments using 371 piglets. Treatments in the first two experiments were formed by the
   factorial arrangement of hydrocortisone (-HYD or +HYD) and limited nursing (-LN or
   +LN) imposed form d 14 to weaning (d 28). Hydrocorfisone was replaced by
   adrenocorticotropic hormone (ACTH) in the third experiment. Growth rates were severely
   depressed by HYD (P < .01), LN (P < .001) and to a lesser extent (P < .06) by ACTH
   during the last 2 wk of lactation. During the first 14 d postweaning, piglets continued to
   grow more slowly following HYD treatment (P < .01), whereas LN piglets grew more
   rapidly than those allowed to suckle normally. Although piglets were smaller at weaning
   after HYD injection (P < .01), relative weights of liver, pancreas and small intestine were
   increased (P < .05). Only adrenal weights were increased by ACTH (P < .09). Pancreatic
   and intestinal amylase activities were increased two- to three-fold by HYD injection (P <
   .05) but were unaffected by ACTH or LN (P > .10). Sucrase and maltase activity increased
   linearly with age (P < .001). This rate of increase was numerically enhanced by
   glucocorticoid treatment and LN. The normal decrease in lactase activity was accelerated
   by LN and HYD injection, with the greatest depression caused by the combination of LN
   and either HYD or ACTH administration (P < .05). Glucocorticoid administration to
   nursing piglets can evoke premature elevation of the carbohydrase enzymes necessary for
   initiating the hydrolysis of starch.
   (Key Words: Hydrocortisone, ACTH, Limited Nursing, Enzymes, Piglets, Digestive

                                                                            J. Anita. Sci. 1989. 67:2956--2973

                      Introduction                             immediately postweaning. Pancreatic amylo-
                                                               lytic activity is low and constant up to 3 wk of
   Slow development of carbohydrase en-
                                                               age, but a marked increase occurs between d
zymes in early-weaned pigs likely is a
                                                               28 and d 70 of life (Kitts et al., 1956; Coning
contributing factor for the inferior performance
                                                               et al., 1978; Shields et al., 1980a). Intestinal
                                                               sucrase and maltase activities follow a similar
                                                               trend, whereas lactase exhibits an inverse
     1Current address: Monogastric Res. Dept., Purina Mills,   relationship to these two enzymes (Bailey et
Inc.51401 S. Hanley, St. Louis, MO 63144.                      al., 1956; Manners and Stevens, 1972; Au-
    "t.~rrent address: Centro Nacional de lnvestigaciones en   maitre and Coning, 1978). This development
Alimentacion y Nutricion Fisiologia, Instituto Nacional de
Forestals, Agricolas y Pecuarias, Apartado Postal 29A,         sequence closely resembles that in rats (Hen-
Queretaro, Queretaro, Mexico 76020.                            ning, 1981) and mice (Moog et al., 1973).
    3To whom reprint requests should be addressed.                 Carbohydrase induction during the weaning
    4Dept. of Anim. Sci. The assistance of Scott Williamson,   period in rats is dependent on thyroid and
Howard Cook, Steve Heffernan and Dale Alexander with
diet preparation and animal care is gratefully acknowledged.   adrenal integrity (Koldovsky et al., 1974;
    Received July 15, 1988.                                    Kumegawa et al., 1980) and is relatively
    Accepted March 29, 1989.                                   unaffected by carbohydrate intake (Boyle and

                              Downloaded from by guest on December 22, 2011
                     GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                   2957

Koldovsky, 1980; Yeh et al., 1986). Converse-           jected with HYD and allowed to nurse as in
ly, the ingestion of high-carbohydrate diets by         Treatment 3 (+HYD+LN). Originally, four
adult rats results in increased pancreatic              litters were assigned randomly to each treat-
amylase (Johnson et al., 1977) and intestinal           ment based on date of birth. However, one
disaccharidase activities (Kimura et al., 1978;         litter allocated to the LN treatment contained
Bustamante et al., 1981). Furthermore, pancre-          only four piglets and therefore was removed
atic amylase (Saski et al., 1976; Kumegawa et           from the experiment. Both injection and LN
al., 1980) and intestinal disacchaxidases (Doell        treatments were initiated on d 14. Injections
and Kretchmer, 1964; Koldovsky et al., 1965;            were given every other day from d 14 to d 26.
Moog et al., 1973; Celano et al., 1977) can be              The HYD injection was prepared by sus-
induced prematurely in intact rats and mice by          pending hydrocortisone 21-acetate 5 in sterile
glucocorticoid administration. The similar de-          reagent grade glycerol, which then was diluted
velopmental sequence for digestive enzymes in           with an equal volume of sterile saline to obtain
murines and swine suggests a need to investi-           a final concentration of 50 mg HYD/ml and
gate the effects of both endogenous and                  .90% w/v NaCI. All piglets were injected i.p.
exogenous glucocorticoids and solid food                with HYD to provide 25 mg HYD/kg BW or
consumption on digestive development in the             an equivalent volume of the glycerol-saline
piglet.                                                 vehicle.
                                                            Piglets assigned to the LN treatment were
                                                        allowed four 1-h nursing periods per day (24
             Experimental Procedure                     h). These periods were spaced equally at
   Three experiments were conducted to evalu-           6-h intervals. Limited nursing was accom-
ate the effects of hydrocortisone 21-acetate            plished by placing removable partitions in the
(HYD), adrenocorticotropic hormone (ACTH),              farrowing crate to deny pigs access to their
and limited nursing (LN) during late lactation          dams. The partial weaning area supplied 1.17
on piglet digestive enzyme development and              m 2 of floor space to a litter and provided one
postweaning growth. All piglets were cross-             nipple waterer and a source of creep feed for
bred, resulting from mating Chester White               the pigs.
boars with Duroc x Hampshire x Yorkshire                    Within each litter, five piglets were selected
sows that received nutritionally adequate diets         at random 4 d after birth to be used to measure
during gestation. The maternal diet fed during          enzyme development over time. One pig from
lactation has been described previously (Cor-           this group of five was killed on each of the
ley et ai., 1983). Within 24 h of birth, piglets        following days: 7, 14, 21, 28 and 35. All pigs
were weighed, the needle teeth were clipped             alive on d 28 were weaned but remained in the
and an i.m. injection of 150 mg iron dextran            farrowing crate until d 35. On d 35 the
was administered. Male piglets were castrated           remaining pigs were allocated by weight
on the 3rd d of life.                                   within treatment to pen groups and moved to
   Experiment 1. In this experiment, 127                the nursery. Each nursery pen contained five to
                                                        seven pigs and provided 1.48 m 2 of floor
piglets originating from 15 litters were used.
Four treatments were formed by the 2 x 2                space. The nursery pens were located in an
factorial combination of HYD injection and              environmentally regulated room having an
                                                        average temperature of 27~ A conventional
LN. The four treatments were: Treatment 1,
                                                        corn-soybean meal diet formulated to contain
sham-injected with glycerol-saline vehicle and
                                                        1.03% lysine was prepared. Pigs were allowed
allowed to nurse ad libitum during the
                                                        to consume their diet ad libitum from d 14 to d
28-d lactation (-HYD--LN); Treatment 2,
                                                        56. Pig weights were recorded weekly from
injected with HYD and allowed to nurse
                                                        birth to 56 d. Feed intake was measured
normally (+HYD-LN); Treatment 3, sham-
                                                        weekly from d 14 to d 56.
injected with vehicle but allowed to nurse only
                                                            Experiment 2. One hundred forty pigs
1 h in each 6-h period from d 14 to d 28 of
                                                        originating from 16 litters were used in this
lactation (-HYD+LN); and Treatment 4, in-
                                                        growth experiment. Four litters were allotted
                                                        randomly according to birth date to each of the
                                                        four treatments used in Exp. 1. Procedures
  5Crystallinehydrocortisone21-acetate;SigmaChemical    were as in the previous experiment except that
Company,St. Louis, MO (99.4% pure).                     BW gain and feed intake were measured on d

                         Downloaded from by guest on December 22, 2011
2958                                        CHAPPLE ET AL.

14, d 20 and d 28 during lactation. No pigs                during the excision, preparation and weighing
were killed for enzyme measurements. The                   process. Blood samples were centrifuged at
piglets were weaned on d 28, moved to the                  500 x g and plasma was collected. The tissue
nursery on d 35 and weekly weight gain and                 and plasma samples were stored at -20~ until
feed intake were measured for the following 3              analyzed. Preliminary samples in our labora-
wk. In the nursery, pen-groups were formed by              tory have shown virtually no loss of disaccha-
dividing each litter into a light and heavy                ridase activity in intestinal homogenates stored
subgroup.                                                  at this temperature for extended periods (90 d).
    Experiment 3. The four treatments utilized             Kolinska and Semenza (1967) also demon-
in the previous experiments also were used in              strated that intestinal sucrase is quite stable
this experiment. However, ACTH was substi-                 (85% activity retained after storage at 4~ for
tuted for HYD as the injected hormone; it was              4O d).
administered every 4th d rather than every                     Prior to analysis, tissue samples were
other day. Twelve litters involving 104 piglets            thawed at 4~ Samples, including contents, of
were assigned randomly to the four treatments.             intestine about 1 cm in length were taken from
Porcine ACTH 6 was dissolved in a sufficient               6 to 10 (depending on overall length) equally
volume of sterile, isotonic saline to yield a              spaced sites along each intestinal segment. The
final concentration of 60 IU ACTH/ml. This                 samples were finely chopped and mixed and a
solution was injected s.c. in sufficient volume            2-g subsample was suspended in 18 ml of ice-
to provide 15 IU ACTH/kg BW. Pigs not                      cold, distilled water. Both the liver and
assigned to receive ACTH were given a sham                 pancreas were sampled and suspensions were
injection of sterile, isotonic saline.                     prepared in a similar manner, except that only
    One pig selected randomly from each litter              1 g of pancreas was suspended in 19 ml of
 was killed on d 14, d 22 and d 30 for enzyme               water.
measurements. Pigs still alive on d 30 were                     The tissue suspensions were disrupted ini-
 weaned, but they remained in the farrowing                 tially for 15 s in a beaker using a polytron
 crate for an additional 7 d without the dam. On            homogenizer. Each sample then was trans-
 d 37 they were moved as litter groups to the               ferred to a Potter-Elvehjem grinding vessel and
 nursery and weekly growth rate and feed                    further homogenized using six strokes of a
 consumption were monitored for an additional               teflon pestle rotating at 1,000 rpm. The
 3 wk.                                                      resulting homogenates were centrifuged at 500
    Analytical Procedures. Piglets selected for             x g to precipitate cellular debris and connec-
 enzyme measurement were rendered uncon-                    tive tissue. The supernatant fluid then was
 scious by CO2 suffocation. A blood sample                  collected and frozen.
 was obtained by heart puncture and pigs then                   Amylase activity was measured in the
 were killed by exsanguination. The pancreas,               pancreas and small intestinal homogenates 7
 liver and adrenal glands were dissected and                using the starch-iodine method of Howard and
 removed. The small intestine was ligated                    Yudkin (1963). Sucrase, maltase and lactase
 immediately posterior to the pyloric sphincter             activities were determined also to the intestinal
 and anterior to the ileocecal junction to prevent          homogenates (Dahlqvist, 1968). Liver gluta-
 loss of content. The ligated section then was              mate-oxaloacetate transaminase (GOT) activ-
 excised, stripped on mesentery and subdivided              ity was measured by the method of Zuchlewski
 into six segments of equal length. The liver,               and Gaebler (1957). Plasma GOT activity was
 pancreas, adrenals and intestinal segments                  measured as described by Sigma Technical
 were weighed, placed in polyethylene bags and               Bulletin No. 5058 . In each assay, dilutions,
 quick-frozen in a solid CO2-acetone bath. All               and, if necessary, incubation time adjustments
                                                             were made to ensure that assay end-points
 tissue samples were packed in crushed ice
                                                             were within range of linearity with respect to
                                                             time and quantity of enzyme added. All assays
                                                             were conducted within the range of the
     6Grade V porcine adrenocorticotropichormone (65 IU/ standard curves.
 mg) from Sigma ChemicalCompany,St. Louis, MO.                  Statistical Analysis. Data from each experi-
     7"Imestinal"amylasehereafter will be used to identify ment were statistically analyzed using a split-
 the quantityof enzymemeasuredin intestinal homogenates.
 This term is not meant to implysite of synthesis.           plot model in a completely randomized design
     8Sigma Chemical Company,St. Louis, MO.                  (Steel and Torrie, 1980). Each litter during the

                          Downloaded from by guest on December 22, 2011
                     GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                  2959

 suckling period or pen-group during the                response to increased creep feed intake. Al-
nursery phase of Exp. 1 and Exp. 3 was                  though creep feed consumption (d 14 to
considered the whole plot unit to which the             weaning) tended to be higher following impo-
hormonal and limit-nursing treatments were              sition of LN in all experiments reported here,
applied. Time after birth was the sub-plot unit         this effect approached significance only in
for all criteria. This model also was used for          Exp. 1 (P < .14). The HYD-injected pigs
the suckling period of Exp. 2. However,                 consumed increasingly greater quantifies of
because each litter was subdivided by weight            creep feed than did the pigs not injected with
prior to the nursery period, weight group was           HYD in Exp. 1 (HYD x AGE, P < .05), but
the sub-plot unit and time after birth was              the same treatments were without effect in
considered the sub-sub-plot. Initial and final          Exp. 2. The injection of ACTH in Exp. 3
BW for the nursery period, where time was not          progressively depressed feed intake (ACTH x
a factor, were analyzed individually as a               AGE, P < .08).
completely randomized design. All weight gain               Unlike the response to either -HYD+LN or
data were subjected to covariance analysis             -ACTH+LN treatments in Exp. 1 and Exp. 3,
using initial weight for a growth period as the        respectively, the injection of either HYD or
covariate. However, adjusted means are pres-           ACTH without imposition of LH produced less
ented only when the regression of weight gain           severe growth depression initially, but subse-
on initial weight was greater than zero (P <           quent differences in weight gain between
.05) and homogeneous among all treatments.             HYD- or ACTH-injected and uninjected pig-
In addition, rather large differences in creep         lets became more pronounced. The compensa-
feed consumption from week to week were                tory response noted earlier for LN piglets
apparent and suggested heterogeneous vari-             offset some of the progressive decline in
ances for this criteria. Therefore, Bartlett's chi-    growth when averaged across LN treatments.
square test of homogeneity was conducted on            Therefore, hormone treatment x age interac-
the partitioned experimental error variances for       tions were not significant and only the main
these data. In all three experiments, experimen-       effects of HYD and ACTH treatment were
tal error was found to be homogeneous (P >             detected (P < .02 and P < .07, respectively).
.10), so data transformation was deemed                    The LN treatment did not affect growth rate
unnecessary.                                           at any period subsequent to d 35 in Exp. 1 and
                                                       2. Growth of normally suckled pigs increased
                     Results                           at a faster rate than growth of LN pigs from d
                                                       37 to d 58 in Exp. 3 (P < .03). The improved
    Weights and feed consumption data for              growth of LN pigs immediately postweaning
Exp. 1, 2 and 3 are presented in Tables 1, 2           was insufficient to overcome preweaning re-
and 3, respectively. All values are means of           ductions, and the main effect of LN averaged
litter or pen-groups for pigs alive at the end of      across hormone treatments was a depression of
each age interval.                                     56-d weight by 1.0 and .7 kg in Exp. 1 and
    In Exp. 1, LN resulted in reduced growth           Exp. 2, respectively (P < .10) and by 2.7 kg in
rates during the 1st wk of the treatment (d 14         Exp. 3 at 58 d (P < .08). The detrimental
to d 21) regardless of hormone treatment;              effects of HYD injection persisted during the
however, piglets partially compensated for this        nursery period (d 35 to d 42) in Exp. 1 and
reduction during the second treatment week (d          Exp. 2 (P < .02 and P < .002, respectively),
21 to d 28) and the 1st wk postweaning (LN x           resulting in 56-d BW that were 3.0 kg (P <
AGE, P < .001). A similar response was                 .02) and 5.9 kg (P < .001) lighter than BW of
observed for LN piglets in Exp. 3 (I_aNx AGE,          uninjected pigs, respectively. Although not
P < .001). Although piglets on treatment               significant (P = .29), pigs injected with ACTH
-HYD+LN in Exp. 2 also exhibited limited               were 1.5 kg lighter th an uninjected pigs at 58
recovery, the growth reduction resulting from          d.
HYD administration was so severe that piglets              In Exp. 1 it appeared that the residual
on treatment +HYD+LN did not (LN x HYD x               stunting effects of HYD injections of post-
AGE, P < .09). Smith (1961) and Thompson et            weaning gain were more severe for heavier
al. (1981) also have reported an initial crop in       than for smaller pigs; thus, this effect was
performance followed by increased gain the             investigated in Exp. 2 by division of litters into
2nd wk of partial weaning and attributed this          light and heavy sub-groups at weaning. Not

                         Downloaded from by guest on December 22, 2011
2960                                     CHAPPLE ET AL.

       0                                           ~          v~ ~   O~         ,..~ r   ~I~   Or~ ~ ' ~ ~ "


                                          .            ~       =~                 ~.           ~




                            +    +                                                        c4





                                              ~ ~~i                       ~ ~                                  ~
                   Downloaded from by guest on December 22, 2011
                                   GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                2961

                                                                    surprisingly, heavier pigs gained more rapidly

                           ++          ~6
                                                                    (P < .001) than lighter pigs during the nursery
                                                                    period (Table 2). However, the disparity
                                                                    between heavy and light sub-groups for both
                 !9        .~ ,n                                    gain and feed intake was considerably less for
                                                                    HYD-injected on LN pigs than that between
                                                                    untreated pigs (-HYD-LN), although sub-
                                                               g    group differences (heavy vs light) in initial
                                                                    weights were similar regardless of treatment
                           ~9                                       (LN x HYD x SIZE, P < . 11 and P < .05 for
                                       +                       +    gain and feed intake, respectively).

                                                                       Efficiency of feed utilization of pigs in+
                                                                    jected with HYD in Exp. 1 improved between
                                                                    35 and 56 d of age, but gain:feed values on
                                                                    uninjected pigs decreased (HYD x AGE, P <
                                                                    .05)9 This compensatory response may be
                                                                    interpreted as a recovery from the detrimental
                                                                    effect of HYD, which is known to depress N
    m.~. .                             v                 ~          retention when pharmacological doses are
                                                                    administered to rats (Varela et al., 1977;
                                                                    Moreiras-Varela et al., 1978)9 Some pen
                                                         1      i I groups in Exp. 2 consumed very little feed and
                                                         msw        lost considerable weight during the 2nd wk
                                                                    postweaning (d 35 to d 42)9 This resulted in
                                                                    very large, negative gain:feed values that
             I                                                      would have distorted treatment means and led
                                                                    to potentially erroneous inferences upon statis-
                                                         = ..~ _~ . tical analysis. Therefore, gain:feed data in
                                                                    Table 2 are simple arithmetic quotients of the
                                                                    gain and feed intake means for each treatment
                                                                    at the various ages and analysis of variance
                                       "~                           was not conducted. Presented this way, pigs
                                                                    responded similarly to those in Exp. 1; feed
                                                                    utilization improved HYD-injected pigs but
                                                                    decreased in uninjected pigs with advancing
                  ~.~ .~.~                                          age. The efficiency of feed utilization during
                                                                    the nursery period was unaffected (P > .15) by
                                                                    prior LN treatment or by prior ACTH treat-
                                                         --       m    Postweaning survival was high in Exp. 1
                                                                    and Exp. 3 with two and zero pigs lost,
                                                                    respectively. However, the severe growth
                                                                    depression following HYD injection prewean-
                                                                    ing in Exp. 2 resulted in 25% mortality when
                                                                    averaged over the +HYD-LN and +HYD+LN
                                                                    treatments. In contrast, all - H Y D - L N and
                 ~ me                                               -HYD+LN piglets in Exp. 2 survived to 56 d
                                                                    of age.
                                       9               .               Total body and organ weights of piglets
                           e~                                       killed for enzyme measurements in Exp. 1 and
                                                                    Exp. 3 are presented in Tables 4 and 5,
%                                                                   respectively. Body weights are included only
                                                                    for reference; organ weights and enzyme
                                       ~.~          x~
                                                "8 < .- ~' x x x activities are expressed per kilogram of BW. In
                                                .~                  both Exp. 1 and Exp. 3 total organ weights
                      '~        ~'~"                                expressed per kilogram are in agreement with
                                                                    the reports of Walker (1959) and Widdowson

                                            Downloaded from by guest on December 22, 2011
2962                              CHAPPLE ET AL.




                                  ~   N                                                N




       <ff                        9               ~   f        ~          ~   ~        ~


                 9     I

             i I§
                 I    "4-   ~'a

       9         I II,.-.I


                                                                      .o Q        ..

             Downloaded from by guest on December 22, 2011
                    GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                        2963

                                                              and Crabb (1976). The relative rates of growth
                                                              were not the same for each tissue, nor were
                                                              they proportional to the total BW increase. All
                                                              four tissues appeared to be spared the stunting
                                                              effect associated with the 1st wk postweaning;
          .~        .'a                                       total weights of these organs continued to
                                                              increase at a relatively constant rate, whereas
                                                              total BW did not.
                                                                  The HYD injections stimulated hepatic and
                                                         t~   pancreatic growth within 7 d (21 d of age) and
                                                              small intestine growth within 14 d (28 d of
                                                              age) after administration (HYD x AGE, P <
                                                              .04; Table 4). This is in agreement with the
                                                              known hypertrophic effects of corticosteroids
                                                              on the pancreas of suckling rats (Morisset et
                                                              al., 1981) and the liver of the growing rat
          _         .'~       ~       ~                 r/)   (Tomas et al., 1979). Although not statistically
                                                              significant, HYD tended to depress adrenal
                                                              weights at both the 14<1 and 21<1 postinjection
                                                              measurements (28 and 35 d of age, respective-
                                                                  Organ weights were unaffected by LN in
                                                              Exp. 1 (P > .10; Table 4), but in Exp. 3 the
                                                              small intestine, liver and adrenal weights,
" ~ t"q            ~-~                ~           ..~
                                                              relative to BW, were increased (Table 5) by
          74~                                           m
                                                              the LN treatment (LN x AGE, P < .05). The
                                                              administration of ACTH stimulated adrenal
                   ~d.~       ~ ~
                                                              growth (Table 5) within the first 8-d period (22
               .   ~              ~       v       ~-          d of age) after administration (ACTH x AGE,
                                                              P < .09).
                                                                  Total enzyme activity expressed per kiloo
                                                              gram of BW (activity/g tissue x tissue weight/
                                                              kg BW) for pancreatic and intestinal tissues is
                   ~;;~       ~       ~           .-~         presented in Tables 6 and 7 for Exp. 1 and
                                                              Exp. 3, respectively. The HYD injections
                   z~,~       ~ '~ o ,,~                      (Table 6) resulted in a two- to three-fold
                                                              increase in pancreatic and intestinal amylase
                                                              activity relative to pigs not receiving hormone
                                                              treatment (HYD x AGE, P < .05). Despite
                                                              random allotment procedures, pigs designated
                                                              to the LN treatments had lower pretreatment (d
          ~,                                                  7 and d 14) amylase activities. Statistically,
          ~        , ,
                   ~"o' - v       ~
                              v' '~ -             v
                                                              this resulted in an apparent overall depression
                   "~         ~               ~               of intestinal amylase by LN (P < .10), which
                                                              probably was not a true effect.
                                                                  The magnitude and direction of sucrase and
                                                              maltase activity changes (Table 6) were similar
                                                              to each other in response to treatment and
                                                              advancing age. Lactase activity exhibited an
                                                         X    inverse relationship to both sucrase and mal-
                                                              tase. This developmental pattern is consistent
                                                              with the normal ontogeny of the pig (Manners
                                                              and Stevens, 1972; Aumaitre and Corring,
                                                               1978) and the mouse (Moog et al., 1973).
                                                              Similar to the situation with amylase, piglets

                          Downloaded from by guest on December 22, 2011
2964                     CHAPPLE     ET   AL.



            [_,   .





            0                                   c,,it ~-   t ' ~ t-.-        ~   t'-,l



       Downloaded from by guest on December 22, 2011
                            GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                   2965

                                                                killed from litters assigned to receive either
                                                                +HYD or +LN had lower pretreatment sucrase
                                                                and maltase activities than those not treated.
                                                                Subsequent to HYD injection (d 14) both
                                                                sucrase and maltase activities increased more
                                                                rapidly and to a higher level. Limited nursing
                                                                alone had little effect on these two enzymes,
 . u q .~-   -9                                                 but when combined with glucocorticoid
                                                                (+HYD+LN), the response was additive (LN x
                                                                HYD x AGE, P < .09 and P < .06 for sucrase
                                                                and maltase, respectively).
                                                                    Pancreatic and intestinal amylase in Exp. 3
                                                 E    "
                                                                (Table 7) increased with advancing age,
                                                                regardless of treatment (P < .02 and P < .05
                                                                for pancreatic and intestinal amylase, respec-
                                                                tively). The LN treatment apparently depressed
                                                                pancreatic amylase (P < .02), but, as in Exp. 1,
                    "~,~     -~ .~                              in which a similar tendency was observed,
                                                                pretreatment activity (d 14) was lower in the
                    ~                ~            o             LN litters. An explanation for the lack of
~ooe,                                                           increase in intestinal amylase activity between
             ~'r,                                               d 22 and d 30 of Exp. 3 (quadratic, P < .01) is
                                                                not apparent. The ACTH treatment, either
                                                                alone or in combination with LN, had little
                                                                effect (P > .10) on either pancreatic or
                                                                intestinal amylase.
                                     ,..~, . ~        ~             The pattern of change in sucrase activity
                                                      r,        was very similar to that for maltase (Table 7).
                    ~ ~.             "= ,.                9     Numerically, both enzymes were elevated on d
                    ~            ~    ~'~             -         22 by both the +ACTH-LN and the
                                                                -ACTH+LN         treatments,     but   not   by
                                                                +ACTH+LN. The LN x ACTH x AGE
                                                                interaction was significant (P < .07) only for
                        ~    ~                   .S   o         sucrase. Lactase activity at d 22 was elevated
                                                                above      -ACTH-LN         levels   by    both
                                                                +ACTH-LN and -ACTH+LN treatments, but
                                                                it also declined more rapidly with age than was
~eqeq                                                           the case in the untreated pigs (LN x ACTH x
                                                                AGE, P < .01).
                                                                    Liver GOT activity by 7 d after glucocorti-
                                                                coid treatment (21 d of age) was twice that of
                                                                uninjected pigs (Table 8) this elevated level
                        -    ~v~;~                    "~
                                                                was maintained after weaning (HYD x AGE, P
                                                                < .001). In contrast, ACTH administration had
                                                 V    ~.~
                                                                no effect (P > .10) on liver GOT activity
                                                                (Table 9). On d 7 +LN piglets in Exp. 1 (Table
                             -       ~=~-~..=                   8) had higher liver GOT activity than - L N
                                                                piglets; however, GOT activity of +LN piglets
                                                                was not different from that of - L N piglets at
                                                 to             any other time (LN x AGE, P < .02). The lack
                                                                of a post-treatment (after d 14) LN effect on
             o~                                                 liver GOT activity was substantiated by results
                                                                of Exp. 3 (Table 9).
                                                                    Plasma GOT decreased linearly (P < .05)
                                                                with age in Exp. 1 (Table 8). In Exp. 3 (Table

                                 Downloaded from by guest on December 22, 2011
2966                                                      CHAPPLE ET AL.

9), p l a s m a G O T t e n d e d to b e h i g h e r o n d 2 2         17 o f age in r e s p o n s e to h o r m o n a l a n d d i e t a r y
a n d l o w e r o n d 3 0 t h a n initial l e v e l s (d 14)           stimuli. T h e a p p e a r a n c e o f cz d i s a c c h a r i d a s e
r e g a r d l e s s o f treamaent. N e i t h e r L N n o r h o r -     a c t i v i t y p r i o r to t h i s age is d e p e n d e n t o n
m o n e t h e r a p y i n f l u e n c e d p l a s m a G O T activity   a d r e n a l i n t e g r i t y a n d can b e i n d u c e d p r e c o -
( P > .10) in e i t h e r e x p e r i m e n t .                        ciously by exogenous glucocorticoid adminis-
                                                                       tration. D i s a c c h a r i d a s e a c t i v i t y is n o t i n f l u -
                                                                       enced           by       oral       ingestion        of      substrate.
                                                                       C o n v e r s e l y , b y 23 d o f age, e n z y m e a c t i v i t y is
   T h e p h y s i o l o g i c a l o n t o g e n y o f the r a t       totally i n d e p e n d e n t o f g l u c o c o r t i c o i d s t i m u l a -
jejunum undergoes an abrupt change about d                             tion, b u t it f l u c t u a t e s in r e s p o n s e to the n a t u r e

                        IMPOSED ON DAY 14 ON PIGLET ORGAN WEIGHTS (EXP. 1)

                         HYD:                                                                            +                            +
Age                      IN:                                                +                                                         +
BW, kg
  7d                                                  1.60                      1.10                          1.75                        1.49
 14 d                                                 3.88                      3.18                          3.85                        3.80
 21 d                                                 6.83                      4.92                          5.35                        4.59
 28 d                                                 8.76                      7.15                          6.13                        5.46
 35 d                                                 8.34                      6.03                          6.86                        6.48
 Mean                                                 5.88                      4.48                          4.79                        4.36
Small intestinal wt, g/kg BWbd
   7d                                                38.8                       30.3                         34.1                         35.9
 14 d                                                35.6                       39.7                         34.5                         32.9
 21 d                                                34.0                       33.1                         34.8                         31.7
 28 d                                                39.0                       35.7                         53.0                         66.3
 35 d                                                49.8                       54.2                         58.4                         67.7
 Mean                                                39.5                       38.6                         43.0                         46.9
Liver wt, g/kg BW bd
   7d                                                31.9                       34.0                         30.1                         35.0
 14 d                                                26.7                       27.9                         26.3                         26.2
 21 d                                                26.2                       24.3                         31.0                         32.9
 28 d                                                25.1                       24.1                         32.5                         34.3
 35 d                                                26.5                       28.3                         28.6                         35.1
 Mean                                                27.3                       27.7                         29.7                         32.7
Pancreas wt, g/kg BWbd
   7d                                                  1.52                      1.75                         1.46                         1.77
 14 d                                                  1.11                      1.06                         1.03                         1.10
 2l d                                                   .95                      1.09                         1.36                         1.47
 28 d                                                  1.15                      1.11                         2.21                         2.24
 35 d                                                  1.69                      1.78                         2.38                         2.69
 Mean                                                  1.28                      1.36                         1.69                         1.85
Adrenal wt, mg/kg BWcd
   7d                                               268                     351                          312                          270
  14 d                                              153                     175                          162                          182
 21 d                                               129                     139                          136                          146
 28 d                                               143                     144                          124                          113
 35 d                                               148                     160                          119                          126
 Mean                                               168                     194                          171                          167
    aRefer to Table 1 for treatment description. Organ weights were determined as removed from the peritoneal cavity,
 subsequent to blotting surface moisture. Intestinal weights include contents.
    bHYD • AGE interaction (P < .001, P < .04 and P < .001 for intestinal, liver and pancreas weights, respectively).
    CLinear (P < .001) and quadratic (P < .05) decrease with age in adrenal weight relative to body weight.
    dWhole plot error mean squares (EMS) are 77.14, 52.99, .1995 and 3,895 and subplot EMS are 39.86, 24.67, .046 and
 2,156 for intestinal, liver, pancreas and adrenal weights, respectively, with 11 and 44 df for each respective pair.

                                   Downloaded from by guest on December 22, 2011
                        GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                            2967

of carbohydrate being consumed (Henning and                  for several reasons: 1) these 2 wk immediately
Sims, 1979; Boyle and Koldovsky, 1980; Yeh                   precede the age at which pigs are known to
et al., 1986). A similar developmental pattern               adjust their enzymic activity in response to
has been reported for rat pancreas amylolytic                dietary change and greatly increase carbohy-
activity (Robberecht et al., 1971; Sasaki et al.,            drase production and 2) any precocious en-
1976; Kumegawa et al., 1980). Although                       zyme induction during the suckling period
Aumaitre (1971) has shown that the exocrine                  could facilitate the transition from an all-milk
pancreas of 5- to 6-wk-old pigs will adapt to                diet to a starch-based, cereal diet normally fed
fluctuations in dietary carbohydrate level,                  at weaning (d 28).
similar to the adaption demonstrated in older                    Total activity and activity per kilogram of
(40 kg) pigs (Corring, 1975), little is known                BW of all enzymes measured, except lactase,
about the dietary or hormonal influences on                  increased with age. When converted to compa-
enzymic development in younger pigs.                         rable units, our values are in agreement with
   Our studies were designed to evaluate the                 those reported by others using similar assay
effect of hormone therapy and substrate induc-               procedures and pigs of similar age (Engstrom
tion on digestive development of pigs during                 et al., 1979; Shields et al., 1980a, b; Graham et
the transition from suckling to postweaning                  al., 1981). We prefer to use total rather than
status. The period from d 14 to d 28 of                      specific activity under our conditions, primar-
suckling was selected as the treatment period                ily because the amount of protein removed by


                                                                Treatment a
                      ACTH:                -                    -                    +                    +
Age                   LN:                  -                    +                    -                    +
BW, kg
 14 d                                           3.68                3.40                  3.48                3.75
 22 d                                           5.83                3.50                  5.32                4.10
 30 d                                           7.92                5.08                  6.08                4.27
 Mean                                           5.81                3.99                  4.96                4.04
Small intestinal wt, g/kg BW bd
 14 d                                          33.0              38.3                    34.1              40.1
 22 d                                          36.9              35.4                    32.5              35.0
 30 d                                          31.6              45.5                    39.6              51.4
 Mean                                          33.8              39.7                    35.4              42.2
Liver wt, g/kg BW bd
 14 d                                          26.2              26.9                 27.2                 26.5
 22 d                                          24.2              25.9                 25.1                 28.1
 30 d                                          23.2              26.9                 26.4                 28.0
 Mean                                          24.5              26.6                 26.2                 27.5
Pancreas wt, g/kg BW d
 14 d                                           1.36                1.24                  1.09                1.17
 22 d                                           1.18                1.30                  1.22                1.21
 30 d                                           1.15                1.33                  1.33                1.37
 Mean                                           1.23                1.29                  1.21                1.25
Adrenal wt, mg/kg BW bcd
 14 d                                      199                  183                  188                  180
 22 d                                      143                  186                  167                  200
 30 d                                      110                  151                  160                  185
 Mean                                      151                  174                  172                  188
   aRefer to Table 3 for treatment description. Organ weights were determined as removed from the peritoneal cavity,
subsequent to blotting surface moisture. Intestinal weights include contents.
   bLN x AGE interaction (P < .05).
   CACTH x AGE interaction (P < .09).
   dWhole plot error mean squares (EMS) are 131.4, 6.539, .0643 and 1,213 and subplot EMS are 27.57, 1.315, .0312 and
637 for intestinal, liver, pancreas and adrenal weights, respectively, with 8 and 16 df for each respective pair.

                              Downloaded from by guest on December 22, 2011
2968                                                            CHAPPLE ET AL.

c e n t r i f u g a t i o n o f w h o l e tissue h o m o g e n a t e s         I n s e r t i o n o f B W i n t o the e x p r e s s i o n o f e n z y m e
can be quite variable. We (preliminary studies)                                activity should provide a better assessment of
and Dahlqvist (1968) have shown that negli-                                    the p i g ' s relative d i g e s t i v e c a p a c i t y b y reflect-
g i b l e q u a n t i t i e s o f e n z y m e activity are l o s t             i n g d i f f e r e n c e s in s p e c i f i c tissue g r o w t h
f o l l o w i n g c e n t r i f u g a t i o n . E x p r e s s i o n o f the    c o m p a r e d to total b o d y g r o w t h .
d a t a as total r a t h e r t h a n as s p e c i f i c a c t i v i t y also         The enzyme assays and units for expressing
c o r r e c t s f o r effects o f h o r m o n e s i n j e c t e d o n          a c t i v i t y w e r e c h o s e n to o b j e c t i v e l y r e p r e s e n t
o r g a n w e i g h t s or p r e s e n c e o f o t h e r p r o t e i n s .     q u a l i t a t i v e c h a n g e s o f e n z y m e q u a n t i t y in

                          AND LIMITED NURING (LN) IMPOSED ON DAY 14 (EXP. 1)

                            HYD:                         -                          -                            +                            +
Age                         LN:                          -                          +                            -                            +
Pancreatic amylase, g starch BW -1 bf
   7d                                         156                                   133                            277                           258
 14 d                                        366                                    225                            358                           285
 21 d                                        589                                    352                            727                         1,020
 28 d                                        584                                    394                          1,320                           791
 35 d                                        738                                    341                          1,488                         1,821
 Mean                                        486                                    289                            834                            849
Intestinal amylase, g starch hydrolyzed.h-l'kg BW-1 bdf
   7d                                          72                                    18                               99                          114
  14d                                         121                                    55                              101                           59
 21 d                                         139                                    71                              170                          177
 28 d                                         193                                   134                              441                          334
 35 d                                         127                                    91                              307                          300
 Mean                                         130                                    74                              224                          197
Sucrase, g sucrose hydrolyzed.- BW -1 cf
 7d                                              1.04                                    .67                               .75                          .92
  14d                                            2.02                                   1.69                           1.56                          1.60
 21 d                                            2.23                                   2.56                           1.68                          1.92
 28 d                                            2.64                                   2.74                           2.74                          2.30
 35 d                                            2.41                                   2.19                           1.74                          3.20
 Mean                                            2.07                                   1.97                           1.69                            1.99
Maltase, g maltose hydrolyzed.h BW -1 cf
   7d                                            2.53                                    1.96                         1.77                         2.10
  14 d                                           5.29                                    4.19                         4.27                         4.06
 21 d                                            6.27                                    6.74                         5.81                         6.72
 28 d                                            8.26                                    7.16                        10.60                         8.57
 35 d                                           11.70                                   10.77                        10.82                        17.13
  Mean                                           6.81                                    6.17                         6.65                         7.72
Lactase, g lactose hydrolyzed-h -l'kg BW-I clef
   7d                                            6.48                                   4.66                         8.20                         6.51
  14 d                                           6.76                                   7.87                         9.56                         7.18
 21 d                                            3.84                                   4.57                         4.34                         2.84
 28 d                                            2.18                                   1.90                         2.64                          .85
  35 d                                            .95                                    .53                         1.09                         1.18
  Mean                                           4.04                                   3.91                         5.16                         3.71
    aRefer to Table 1 for treatment description.
    bHYD x AGE interaction (P < .05 and P < .001 for pancreatic and intestinal amylase.
    ClN • AGE interaction (P < .09 and P < .06 for sucrase and maltase).
    diN from d 14 to 28 depressed intestinal amylase (P < .10) and lactase (P < .09) activities.
    eLinear (P < .001) decrease with age.
    fWhole plot error mean squares (EMS) are 310,591, 10,019, .6997, 5.405 and 3,253 and subplot EMS are 263,022, 3,511,
.2972, 2.836 and 3.057 for pancreatic aamylase, intestinal amylase, sucrase, maltase and lactase, respectively, with 11 and44
df for each respective pair.

                                      Downloaded from by guest on December 22, 2011
                         GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                                    2969

response to the treatment applied. For infer-                    hydrolytic capacity for a specific substrate. To
ences regarding differences between treatments                   correlate enzyme activity measured by our
to be valid, the assay itself cannot be a limiting               methods with quantitative digestibility and
factor to response measurement. This restric-                    absorbability requires more detailed investiga-
tion dictates that assay conditions such as                      tion.
substrate concentration, pH and buffering                           The LN treatment was included to encour-
capacity must be optimized. Obviously, opti-                     age early consumption of dry feed and provide
mal conditions do not occur within the lumen                     an opportunity to establish the presence or
of piglet small intestine. For example, one can                  absence of the substrate induction phenomenon
compute from data presented in Tables 4 and 6                    at this age. Although creep feed consumption
that, on average, even pretreated, 14-d-old                      was increased numerically by LN in all
piglets potentially could hydrolyze 7.5 kg of                    experiments, the main effect was never signifi-
starch daily; this clearly is an unreasonable                    cant (P > .10). This could have been due to
deduction. This calculation demonstrates that                    poor acceptability of the diet (Smith, 1961;
the in vitro values presented herein should not                  Thompson et al., 1981), but equally important
be misinterpreted as estimates of in vivo                        was the litter-to-litter variability of feed

                      AND LIMITED NURSING (LN) IMPOSED ON DAY 14 (EXP. 3)

                                                                    Treatment a
                      ACTH:                   -                      -                      +                      +
Age                   LN:                     -                      +                      -                      +
Pancreatic amylase, g starch hydrolyzed-h-l-kg BW -1 bce
  14 d                                      242                      177                    183                    132
 22 d                                       387                      231                    411                    192
 30 d                                       445                      255                    738
 Mean                                       358                      221                    444                    189
Intestinal amylase, g starch hydrolyzedh-l-kg BW -1 ce
  14 d                                        43                      86                     97                     84
 22 d                                       243                      126                    203                    187
 30d                                         116                     131                    215                    133
 Mean                                        134                     114                    172                    135
Sucrase g sucrose BW -1 de
  14 d                                         1.94                       1.87                  2.08                   1.80
 22 d                                          2.54                       3.26                  3.24                   2.01
 30 d                                          3.03                       3.06                  2.37                   2.71
 Mean                                          2.50                       2.73                  2.56                   2.17
Maltase, g maltose hydrolyzedh- 1-kg BW -1 ee
  14 d                                         4.34                       4.44                   4.46                  4.55
 22 d                                          6.29                       7.61                   8.61                  5.70
 30 d                                         11.08                      11.43                  11.52                  9.09
 Mean                                          7.24                       7.83                   8.19                  6.45
Lactase, g lactose hydrolyzed.h BW -1 de
  14 d                                         7.98                      7.47                   6.48                   7.62
 22 d                                          3.49                      5.04                   5.94                   1.89
 30 d                                          2.02                      1.34                   2.27                   1.25
 Mean                                          4.50                      4.62                   4.90                   3.58
   aRefer to Table 3 for treatment description.
   bLN from d 14 to d 30 depressed pancreatic amylase (P < .02).
   CLinear increase (P < .02) of pancreatic amylase and linear (P < .05) and quadratic (P < .01) increase of intestinal amylase
and linear (P < .001) increase of mahase activities with age.
   diN x ACTH x AGE interaction (P < .07 and P < .01 for sucrase and lactose, respectively).
    ewhole-plot error mean squares (EMS) are 43,484, 8,003, .4215, 6.759 and 4.117 and subplot EMS are 49,452, 5,362,
.3231, 4.393 and 1.600 for pancreatic amuylase, intestinal amylase, sucrase, maltase and lactase, respectively, with 8 and 16
df for each respective pair.

                             Downloaded from by guest on December 22, 2011
2970                                                               CFIAPpLE ET AL.


                             HYD:                          -                           -                           +                            +
Age                          LN:                           -                           +                           -                            +
Liver GOT, gmol OAA produced-min-lkg BW -1 bee
  7d                                      94                                           125                           79                         144
 14 d                                     74                                            79                           65                          59
 21 d                                     59                                            53                          110                         158
 28 d                                    108                                            81                          233                         206
 35 d                                     97                                           114                          191                         190
 Mean                                     86                                            90                          136                         151
Plasma GOT, Sigma Frankel units/ml plasmade
  7d                                      39.0                                           41.0                          23.5                         31.5
 14 d                                     24.5                                           29.7                          24.5                         24.5
 21 d                                     19.0                                           15.7                          27.3                         19.8
 28 d                                     20.8                                           17.0                          18.5                         21.3
 35 d                                     21.0                                           23.7                          23.5                         36.0
 Mean                                     24.9                                           25.4                          23.5                         26.6
    aRefer to Table 1 for treatment description.
    bHYD x AGE interaction (P < .001).
    ClN x AGE interaction (P < .02).
    dLinear decrease (P < .05) with age.
    eWhole-plot error mean squares (EMS) are 1,151 and 107 and subplot EMS are 876 and 164 for liver GOT per kg BW and
plasma GOT activities, respectively, with 11 and 44 df for each respective pair.

c o n s u m p t i o n r e g a r d l e s s o f t r e a t m e n t ; this m a d e     M a n n e r s a n d S t e v e n s ( 1 9 7 2 ) r e p o r t e d a ten-
d e t e c t i o n o f s i g n i f i c a n t e f f e c t s difficult. T h e         d e n c y for artificially r e a r e d p i g l e t s to h a v e
v a r i a t i o n in p a n c r e a t i c a m y l o l y t i c a c t i v i t y o f   h i g h e r sucrase a n d l o w e r lactase l e v e l s t h a n
u n i n j e c t e d p i g l e t s a p p e a r e d to b e m o r e a                 t h o s e n u r s e d b y the sow. H o w e v e r , o u r r e s u l t s
f u n c t i o n o f litter o f o r i g i n t h a n o f s o l i d f o o d           are in a g r e e m e n t w i t h t h o s e o f H a r t m a n
consumption. Conflicting data have been pub-                                       (1961), w h o f o u n d n o d i f f e r e n c e in the
l i s h e d w i t h r e g a r d to the e f f e c t o f s u b s t r a t e           d e v e l o p m e n t o f a m y l a s e or cx a n d [3 d i s a c c h a r i -
i n g e s t i o n o n c a r b o h y d r a s e i n d u c t i o n in piglets.        d a s e activity b e t w e e n p i g l e t s w e a n e d o n d 7

                           AND LIMITED NURSING (LN) IMPOSED ON DAY 14 (EXP. 3)

                              ACTH:                         -                           -                           +                            +
Age                           LN:                           -                           +                           -                            +
Liver GOT, gmolOAAproduced.min-lkg BW-1 b
 14 d                                   80                                             80                           70                           84
 22 d                                   81                                             56                           82                           85
 30 d                                  70                                              85                           85                           90
 Mean              77                  74                                              79                           86
Plasma GOT, Sigma Frankelunits/ml plasmab
 14 d                                   18.3                                            27.3                        24.0                         31.0
 22 d                                   24.3                                            39.7                        29.0                         33.7
 30 d                                   25.7                                            25.3                        12.3                         17.0
 Mean                                   22.8                                            30.8                        21.8                         27.2
    aRefer to Table 3 for treatment description.
    bWhole-plot error mean squares (EMS) are 471 and 78.4 and subplot EMS are 305 and 23.3 for liver GOT per kg BW and
plasma GOT activities, respectively, with 8 and 16 df for each respective pair.

                                        Downloaded from by guest on December 22, 2011
                    GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                  2971

and those allowed to nurse without access to           iological age or developmental stage of the
dry feed.                                              intestine is less discretely associated with
    Using LN as a method of stimulating food           chronological age in the neonatal piglet than is
consumption may have caused confounding                true for rat pups. It also appears that from 14
due to an elevated endogenous glucocorticoid           to 28 d of age, piglet t~ disaccharidase
secretion rate. Blatchford et al. (1978) have          development is not wholly dependent on
shown that frustration, caused by interrupting a       glucocorticoid or substrate induction, whereas
learned operant response, elevated plasma              the exocrine pancreas can be substantially
ACTH and corticosteroid levels in young pigs.          stimulated by glucocorticoid. The hypothesis
However, the enzymes that were induced most            that the development of these tissues is under
dramatically by exogenous HYD in our studies           the control of some other endocrine system
(amylase and hepatic GOT) were not stimu-              cannot be disregarded, because thyroxine is
lated by LN. This suggests that the adrenal            known to play at least a permissive role in the
response associated with the stress of the LN          glucocorticoid induction of rat jejunal sucrase
treatment did not provide the same response as         (Henning, 1978) and it has not yet been
that observed from exogenous HYD injections.           established that perinatal enterocytes of piglets
   Although directional changes were similar,          are specific target cells of glucocorticoids at
the magnitude of response of intestinal sucrase        all.
and maltase to HYD injection was relatively                 Growth-stunting effects associated with
minor compared with the two- or three-fold             continuous corticoid administration have been
increase in pancreatic amylase and hepatic             documented in rats (Ingle, 1941; Winter et al.,
GOT activity after this treatment. Because             1950) and guinea pigs (Hausberger and Ram-
HYD administration resulted in a marked                say, 1955). These studies were confined t o .
hypertrophic effect for all three organs, it was       animals during the late growth stage (200- to
surprising that only hepatic and pancreatic            300-g rats and 500- to 600-g guinea pigs,
enzyme activities were increased.                      respectively) and showed that the growth
   The relatively small response of sucrase and        depression mediated b y corticosteroids was
maltase to HYD injection is in contrast to rat         reversible upon termination of treatment. How-
studies, in which sucrase generally is the most        ever, a single injection of cortisone to
sensitive indicator for glucocorticoid induction       4-d-old rats pups has been shown to result in
of intestinal enzymic capacity (Henning and            poor growth that remained evident at 84 d
Sims, 1979). Although similarities exist be-           (Sobel, 1978) and 120 d (Ioachim, 1971). This
tween these species in the development of              effect was attributed to accelerated skeletal
intestinal disaccharidases, some distinct differ-      ossification and reduced long bone growth.
ences also are apparent. Normally suckled rats         Our results resembled the findings of Ingle
have nearly undetectable amounts of sucrase            (1941) and Winter et al. (1950). The growth
activity until d 15 or d 16. Within approxi-           depression resulting from HYD treatment,
mately 10 d after appearance, sucrase activity         although prolonged, was reversible.
reaches an adult level, which coincides with                The mechanism of growth retardation by
the age at which weaning is complete (Hen-             HYD or LN evidently is different, because the
ning, 1981). Conversely, sucrase activity of           treatment effects were additive when com-
neonatal piglets is comparably low up to d 7.          bined. Piglets injected with HYD exhibited a
A large increase occurs by d 14, with a much           more gradual decrease in daily gain still
more gradual increase thereafter (Bailey et al.,       evident after weaning, but there was partial
1956; Hartman et al., 1961; Manners and                recovery by 56 d of age. The growth rate of
Stevens, 1972; Aumaitre and Corring, 1978).            LN piglets was dramatically depressed within
These and our own data indicate that piglets of        the first post-treatment week, followed by a
the same age and weight during this develop-           subsequent compensatory period that contin-
mental period varied greatly in their capacity         ued for the 1st wk postweaning.
to hydrolyze sucrose. The appearance of                    The postweaning gain:feed ratio of piglets
sucrase activity in rat pups normally occurs on        injected with HYD was. depressed initially,
the same day of life for all pups and is more          but, like gain, it approached normal values by
consistent from one animal to the next and             8 wk of age. Winter et al. (1950) observed a
from one day to the next during the induction          similar depression in feed efficiency of rats
process. Our observations suggested that phys-         and attributed it to an increased rate of fat

                        Downloaded from by guest on December 22, 2011
2972                                       CHAPPLE ET AL.

deposition in response to glucocorticoid ad-                               Literature Cited
ministration. Tomas et al. (1984) have shown           Aumaitre, A. 1971. Le developpemem des enzymes dans le
that protein accretion rates are reduced in                 tube digestif du jeune porcelet (Importance pour le
corticoid-treated rats. These effects suggest               sevrage et signification nutritionelle). Ann. Zootech.
that energetic inefficiency may be an explana-              (Paris) 20:551.
                                                       Aumaitre, A. and T. Corring. 1978. Development of
tion for the reduced gain:feed values. In                   digestive enzymes in the piglet from birth to 8 weeks.
contrast, -HYD+LN and - H Y D - L N piglets                 II. Intestine and intestinal disaccharidases. Nutr.
were equally efficient at converting feed to                Metab. 22:244.
gain after weaning. This indicates that the            Bailey, C. B., W. D. Kitts and A. J. Wood. 1956. The
                                                            development of the digestive enzyme system of the pig
growth depression resulting from LN during
                                                            during its preweaning phase of growth. B. Intestinal
lactation was a transient effect of nutrient                lactase, sucrase and maltase. Can. J. Anim. Sci. 36:51.
deprivation, unlike the response that resulted         Blatchford, D., M. Holzbauer, D. L. Ingrain and D. F.
from the abnormal hormonal levels created by                Sharman. 1978. Responses of the pituitary-adrenal
HYD injection.                                              system of the young pig to environmental changes and
                                                            drugs. Br. J. Pharmacol. 62:241.
     It is difficult to explain the absence of         Boyle, J. T. and O. Koldovsky. 1980. Critical role of adrenal
response to ACTH. Blatchford et al. (1978)                  glands in precocious increase in jejunal sucrase
demonstrated that doses lower than those used               activity following premature weaning in rats: negli-
in our studies were sufficient to stimulate                 gible effect of food intake. J. Nutr. 110:169.
                                                       Bustamante, S., M. Gasparo, K. Kendall, P. Coates, S.
adrenal secretion of cortisol in piglets. Howev-
                                                            Brown, B. Somawane and O. Koldovsky. 1981.
er, the half-life of ACTH and the resultant                 Increased activity of rat intestinal lactase due to
endogenous cortisol is very short (Sebranek et              increased intake of tt-saccharides (starch, sucrose) in
al., 1973). Thus, stimulus of the target tissues             isocaloric diets. J. Nutr. 111:943.
may have been very insufficient. In contrast,          Celano, P., J. Jumawan, C. Horowitz, H. Lau and O.
                                                             Koldovsky. 1977. Prenatal induction of sucrase
 the 21-acetate form of hydrocortisone is slowly             activity in rat jejunum. Biochem. J. 162:469.
 absorbed when injected peritoneally (Sobel,           Corley, J. R., M. W. Each, J. M. Bahr and R. A. Easter. 1983.
 1978) and would be expected to elevate                      Amino acid supplementation of low-protein diets for
 circulating glucocorticoid levels chronically.              swine: effects of gestation treatment on reproduction
 Further studies are needed to determine the                 performance of gilts and sows. J. Anim. Sci. 56:108.
                                                       Corring, T. 1975. Adaptation de la secretion du pancreas
 injection frequency and(or) dosage of both                  exocrine au regime alimentaire chez le porc,
 hormones necessary to induce the enzyme                     physiologie comparee, etude experimentale et
 capacity observed in the present work.                      mecanisa'nes. Thesis Doct. Etat Sci., Nat., Paris, VI.
     We have shown that HYD injections (25             Corring, T., A. Aumaitre and G. Durand. 1978. Develop-
                                                             ment of digestive enzymes in the piglet from birth to 8
 mg/kg BW each) administered every other day                 weeks. I. Pancreas and pancreatic enzymes. Nutr.
 for the last 2 wk of suckling greatly increased             Metab. 22:231.
 pancreatic amylolytic activity of piglets. The        Dahlqvist, A. 1968. Assay of intestinal disaccharidases.
 intestinal disaccharidases were only slightly               Anal. Biochem. 22:99.
                                                       Doell, R. G. and N. Kretchmer. 1964. Intestinal invertase:
 responsive to HYD. Because of the extreme
                                                             precocious development of activity after injection of
 catabolic action of HYD, any beneficial effect              hydrocortisone. Science 143:42.
 that might have been afforded by an improved          Engstrom, M. A., K. E. Ekstrom and D. C. Malaan. 1979.
 enzymic capacity apparently was offset by the                Intestinal disaccharidase activities of three breeds of
 resultant growth depression. However, it is                  swine. J. Anita. Sci. 48:1349.
                                                       Graham, P. L., D. C. Mahan and R. G. Shields, Jr. 1981.
 possible that smaller or less frequent doses                 Effect of starter diet and length of feeding regimen on
 could elicit the desired enzyme induction                    performance and digestive enzyme activity of
 without retarding growth substantially. Limited              2-week-old weaned pigs. J. Anita. Sci. 53:299.
 nursing tended to increase the consumption of          Hartman, P. A., V. W. Hays, R. O. Baker, L. H. Neagle and
                                                              D. V. Catron. 1961. Digestive enzyme development in
  creep feed and the starter diet the 1st wk
                                                              the young pig. J. Atom. Sci. 20:114.
 postweaning but had no effect on carbohydrase          Hausberger, F. X. and A. J. Ramsay. 1955. Steroid diabetes
 activity. Although not conclusive, our results               in guinea pigs: effects of hydrocortisone administra-
  indicate that from 14 to 28 d of age the                    tion on blood and urinary glucose, nitrogen excretion,
 digestive enzymes of piglets are insensitive to              fat deposition, and the islets of Langerhans. Endocri-
                                                              nology 56:533.
  substrate induction, at least to the extent that      Helming, S. J. 1978. Permissive role of thyroxine in the
  LN increased the consumption of those sub-                  ontogeny of jejunal sucrase. Endocrinology 102:9.
  strates. Adrenocorticotropic hormone did not          Henning, S. J. 1981. Postnatal development: coordination of
  stimulate digestive enzymic activity.                       feeding, digestion and metabolism. Am. J. Physiol.

                         Downloaded from by guest on December 22, 2011
                          GLUCOCORTICOIDS AND CARBOHYDRASE DEVELOPMENT                                                        2973
      241:G199.                                                          growing rats by dexamethasone. Biochim. Biophys.
Henning, S. J. 1979. Delineation of the glucocortieoid-                  Acta 428:619.
      sensitive period of intestinal development in the rat.       Sebranek, J. G., D. N. Marple, R. G. Cassens, E. J. Briskey
      Endocrinology 104:1158.                                            and L. L. Kastenschmidt. 1973. Adrenal response to
Howard, F. and J. Yudkin. 1963. Effect of dietary change                 ACTH in the pig. J. Anita. Sci. 36:41.
      upon the amylase and trypsin activities of the rat           Shields, R. G., Jr., K. E. Ekstrom and D. C. Mahan. 1980a.
      pancreas. Br. J. Nutr. 17:281.                                     Effect of weaning age and feeding method on digestive
Ingle, D. J. 1941. The production of glyeosuria in the normal            enzyme development in swine from birth to ten weeks.
      rat by means of 17-hydroxy-ll-dehydoreorticos-                     J. Anim. Sci. 50:257.
      terone. Endocrinology 19:649.                                Shields, R. G., Jr., D. C. M ahaa and K. E. Ekstrom. 1980b.
loachim. H. L. 1971. The cortisone induced wasting disease               Effect of moderate or severe protein restriction during
      of newborn rats: histopathological and autoradio-                  pregnancy on sow and progeny digestive enzymes. J.
      graphic studies. J. Pathol. 104:201.                               Nutr. 110:1507.
Johnson, A., R. Hurwitz and N. Kretchmer. 1977. Adapta-            Smith, D. M. 196l. The effect o f daily separation of sows
      tion of rat pancreatic amylase and chymotrypsinogen                from their litters upon milk yield, creep intake and
      to change in diet. J. Nutr. 107:87.                                energetic efficiency. N. Z. J. Agric. Res. 4:232.
Kimura, T., A. Seto and A. Yoshida. 1978. Effect of diets on       Sobel, E. H. 1978. Effects of neonatal stunting on the
      intestinal disaccharidase and leucineaminopeptidase                development of rats: early and late effects of neonatal
      activities in refed rats. J. Nutr. 108:1087.                       cortisone on physical growth and skeletal maturation.
Kitts, W. D., C. B. Bailey and A. J. Wood. 1956. The                     Pediatr. Res. 12:945.
      development of the digestive enzyme system of the pig        Steel, R.G.D. and J. H. Torrie. 1980. Principles and
      during its pre-weaning phase of growth. A. Pancreatic              Procedures o f Statistics: A Biometrical Approach (2nd
      amylase and lipase. Can. J. Anim. Sci. 36:45.                      Ed.). McGraw-HiU Book Co., New York.
Koldovsky, O., V. Jirsova and A. Heringova. 1965. Effect of        Thompson, L. H., K. J. Hartford and A. H. Jensen. 1981.
      aldosterone and corticosterone on ~-galactosidase and              E.~-us and fertility in lactating sows and piglet
      invertase activity in the small intestine in rats. Nature          performance as influenced by limited nursing. J. Anim.
      206:300.                                                           Sci. 53:1419.
Koldovsky, O., J. Jumawan and M. Palmieri. 1974.                   Tomas, F. M., H. N. Munro and V. R. Young. 1979. Effect of
      Thyroxine-evoked precocious decrease of acid hydro-                glucocorticoid administration on the rate of muscle
      lases in the ileum of suckling rats. Proc. Soc. Exp. Biol.         protein breakdown in vivo in rats, as measured by
      Med. 146:661.                                                      urinary excretion of Nt-methylhistidine. Biochem. J.
Kolinska, J. and G. Semenza. 1967. Studies on intestinal                 178:139.
      sucrase and on intestinal sugar transport. V. Isolation      Tomas, F. M., A. J. Murray and L. M. Jones. 1984.
      and properties of sucrase-isomaltase from rabbit small             Modification of glucocorticoid-induced changes in
      intestine. Biochim. Biophys. Acta 146:181.                         myofibrillar protein turnover in rats by protein and
Kumegawa, M., N. Maeda, T. Yajima, T. Takuma, E. Ikeda                   energy deficiency as assessed by urinary excretion of
      and H. Hanai. 1980. Permissive role of L-thyroxine in              Nt-methylhistidine. Br. J. Nutr. 51:323.
      induction of pancreatic amylase by cortisol in neonatal      Varela, G., M. V., Mejias, M. de la Higuera and G. Urbano.
      rats. J. Endocrmol. 86:497.                                        1977. Dietary protein, cortisol and fetal growth. Nutr.
Manners, M. J. and J. A. Stevens. 1972. Changes from birth               Metab. 21 (Suppl. 1):215.
      to maturity in the pattern of distribution of lactase and    Walker, D. M. 1959. The development of the digestive
      sucrase activity in the mucosa of the small intestine of           system of the young animal. I. Tissue weights, dry
      pigs. Br. J. Nutr. 28:113.                                         matter of tissues, total acidity and chloride content of
Moog, F., A. E. Denes and P, M. Powell. 1973. Disacchari-                stomach contents in the young pig. J. Agfic. Sci. 52:
      dases in the small intestine o f the mouse: normal                 352.
      development and influence of cortisone, actinomycin          Widdowson, E. M. and D. E. Crabb. 1976. Changes in the
      D, and cycloheximide. Dev. Biol. 35:143.                           organs of pigs in response to feeding for the first 24 h
Moreiras-Varela, O., G. Varela and M. de la Higuera. 1978.               after birth. I. The internal organs and muscles. Biol.
      Cortisol effects on protein utilization in growing rats.           Neonat. 28:261.
      Proc. Nutr. Soc. 37:90A.                                     Winter, C. A., R. H. Silber and H. C. Stoerk. 1950.
Morisset, J., L. Jolicoeur, P. Genik and A. Lord. 1981.                  Production of reversible hyperadrenocortinism in rats
      Interaction of hydrocortisone and caerulein on pancre-             by prolonged administration of cortisone. Endocrinol-
      atic size and composition in the rate. Am. J. Physiol.             ogy 47:60.
      241:G37.                                                     Yeh, K. -Y., F. W. Du and P. R. Holt. 1986. Endogenous
Robberecht. P., M. Deschodt-Lanckman, J. Camus, J.                       corticosterone rather than dietary sucrase as a modula-
      Bruylands and J. Christophe. 1971. Rat pancreatic                  tor for intestinal sucrase activity in artifically reared rat
      hydrolases from birth to weaning and dietary adapta-               pups. J. Nutr. 116:1334.
      tion after weaning. Am. J. Physiol. 221:376.                 Znchlewski, A. C. and O. H. Gaebler. 1957. Changes in
Sasaki, R., M. Mura, T~ Takeuchi, C. Furihata, T.                        activity of transaminases and L-glutamic acid dehy-
      Matsushima and T. Sugimara. 1976. Premature induc-                 drogenase induced by growth hormone. Arch. Bit-
      tion of amylase in pancreas and parotid gland of                   chem. Biophys. 66:463.

                              Downloaded from by guest on December 22, 2011
Citations                         This article has been cited by 2
                                  HighWire-hosted articles:

            Downloaded from by guest on December 22, 2011

Shared By: