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Endocrine __system

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					Chapter 11,
ENDOCRINE
SYSTEM
Section 1 Introduction
I. Organization of Endocrine System
The functions of the body are regulated by the
  nervous and the endocrine system.
The endocrine system consists of endocrine
  glands and cells that secrete hormones in
  various tissues.
Endocrine glands: Glands that do not use ducts
to convey the secretion to a neighboring target,
they are also called ductless glands.
The secretions, known hormones, circulate all
over the body in the blood but may produce
effects only in selected sites.
The target organ(s) may or may not be near the
site of production of the hormone.
A hormone –
  --chemical substance
  --is secreted into the internal body fluids by
one specialized cell or a group of cells and
  --has a physiological control effect on other
cells of the body.
    II. Endocrine vs. Nervous Syste

 Major communication systems in the body
 Integrate stimuli and responses to changes
  in external and internal environment
 Both are crucial to coordinated functions of
  highly differentiated cells, tissues and
  organs
 Unlike the nervous system, the endocrine
  system is anatomically discontinuous.
Nervous system

  •The nervous system exerts
  point-to-point control through
  nerves, similar to sending
  messages by conventional
  telephone.

  •Nervous control is electrical in
  nature and fast.
 Hormones travel via the
bloodstream to target cells
    •The endocrine system broadcasts its
    hormonal messages to essentially all
    cells by secretion into blood and
    extracellular fluid.
    •Like a radio broadcast, it requires a
    receiver to get the message –
    •in the case of endocrine messages, cells
    must bear a receptor for the hormone
    being broadcast in order to respond .
III. Transportation of Hormones
1, Endocrine, or telecrine: glands or
specialized cells release hormones into the
circulating blood that influence the function of
cells at another location in the body.
   Transportation of Hormones
2, Neuroendocrine:
neurons secrete
substances
(neurohormones) that
reach the circulating
blood and influence the
function of cells at
another location of the
body.
       Transportation of Hormones
3. Paracrine, in which cells secret substances
that diffuse into the extracellular fluid and affect
neighboring cells.
IV. Classification of Hormones
1. Proteins and Polypeptides, including hormones
   secreted by the anterior and posterior pituitary
   gland, the pancreas (insulin and glucagon), the
   parathyroid gland (parathyroid hormone), and many
   others.
2. Steroids secreted by the adrenal cortex (cortisol
   and aldosterone), the ovaries (estrogen and
   progesterone), the testes (testosterone), and the
   placenta (estrogen and progesterone)
3. Derivatives of the amino acid tyrosine,
   secreted by the thyroid (thyroxine and
   triiodothyronine) and the adrenal medullae
   (epinephrine and norepinephrine)
V. Properties of the hormone effect
1. Specificity
The special feature of the the target cells is the
  presence of receptors which can “attract” and
  interact with the hormone.
The receptors may be present either on the
plasma membrane, or in the cytoplasm, or in the
nucleus.
These receptor molecules are protein in nature
and may contain carbohydrate or phospholipid
moieties.
2. Signal Transmission
The role of the hormones is to transit the
regulatory signals from the control (endocrine)
system to the target cells (organs or glands).
It could enhance or inhibit some function of the
target.
3. High Biological Efficiency
Low plasma concentration (nmol – pmol/L)
great regulatory function
Signal
amplification
during the
transmembrane
and
intracellular
transmission
4. Interaction Between the Hormones
(1) Synergistic effects. When two or more
hormones work together to produce particular
result their effect are said to be synergistic.
These effects may be additive or complementary.
Additive: Same effect of the hormones on one
target organ, for example, epinephrine and
norepinephrine on the heart rate
Complementary: Work on different stages of a
physiological procedure, for example, FSH
(initiation) and testosterone (maintenance) on
spermatogenesis
(2) Permissive effect. A hormone is said to have a
permissive effect on the action of a second hormone
when it enhances the responsiveness of a target
organ to the second hormone or when it increases
the activity of the second hormone.
Estrogen – Expression of progesterone receptors on
uterus – progesterone effect on the uterus.
Glucocorticoids – effects of catecholamines on
cardiovascular system
(3) Antagonist Effects. In some situations the actions
of one hormone antagonize the effects of another.
Lactation during pregnancy is prevented because the
high concentration of estrogen in the blood inhibits
the milk secretion and action of prolactin.
VI. Mechanisms of Hormonal Action
The first step of a hormone’s action is to bind to
  specific receptors at the target cell.
Locations for the different types of hormones:
1) On the surface of the cell membrane.
   protein, peptide, and catecholamine hormones
2) In the cell cytoplasm.
   steroid hormones
3) In the cell nucleus.
   thyroid hormones (T and T )
1.Second Messenger Mechanisms for
Mediating Intracellular Hormonal Functions

Hydrophilic hormones (proteins, peptides and
catecholamine)
--bind the receptors on the membrane,
--activate some enzyme on the membrane,
-- regulate the concentration of some messengers
(second messengers) in the cytoplasm. .
There are at least three kinds of second
messengers: cAMP, Calcium ions and products
of membrane phospholipid metabolism.
2. Hormones That Act Mainly on the Genetic
   Machinery of the Cell

(1)Steroid
   hormones
   increase protein
   synthesis
(2) Thyroid
   hormones
   increase gene
   transcription in
   the cell nucleus
Section 2 The Pituitary Hormones and Their
Control by the Hypothalamus
I. Anatomical and
   Functional
   Connection
   Between the
   Hypothalamus
   and Pituitary
(hypothalamo-
   hypophyseal
   portal system and
   tract)
Location of the Pituitary
         1. The Pituitary Gland
Anterior
pituitary,
also known
as the
adenohypop
hysis,
Important peptide hormones that secreted by
the anterior pituitary and the targets:
TSH, Thyroid
stimulating hormone
ACTH,
Adrenocorticotropin
hormone
FSH, Follicle-
stimulating hormone
LH, Luteinizing
hormone
MSH, Melanophore-
stimulating hormone
GH, Growth
Hormone;
PRL, Prolactin
The posterior pituitary, also known as the
neurohypophysis.
Two important peptide hormones that secreted
by the posterior pituitary,
ADH
(or vasopressin)
oxytocin
2. Relationship Between the Hypothalamus and
Anterior Pituitary
Neurons in
the
hypothalamus
secreted
releasing
hormones
into the blood
vessels of the
hypothalamo-
hypophyseal
portal system.
These releasing hormones regulate the anterior
pituitary to secrete its hormones in the general
circulation.
3. Hormones Secreted by the Hypothalamus and
Their Effects on Anterior Pituitary
Corticotropin-releasing hormone (CRH) – Stimulates
secretion of ACTH (adrenocorticotropic hormone)
Gonadotropin-releasing hormone (GnRH) Stimulates
secretion of FSH (follicle-stimulating hormone) and LH
(luteinizing hormone)
Thyrotropin-releasing hormone (TRH)-stimulates
secretion of TSH (thyroid-stimulation hormone)
Melanocyte-stimulating hormone release inhibiting
factor (MIF)-inhibits secretion of MSH (Melanocyte-
stimulating hormone)
Melanocyte-stimulating hormone releasing factor
(MRF)-stimulate secretion of MSH
Growth hormone release inhibiting hormone (GHRIH)
or Somatostatin (SS) – inhibits secretion of growth
hormone
Growth hormone-releasing hormone (GHRH)–
stimulates growth hormone secretion
Prolactin-inhibiting factor (PIF)- inhibits prolactin
secretion
Prolactin-releasing factor (PRF)-stimulates prolactin
section
4. Hormones Secreted
from the Posterior
Pituitary
vasopressin and
oxytocin
 produced in neuron
cell bodies within the
supraoptic and
paraventricular nuclei
of the hypothalamus
transported to the posterior pituitary by nerve fibers of
the hypothalamo-hypophyseal tract.
II. Physiological Function of Hormones
Secreted From Anterior and Posterior Pituitary
1.Growth Hormone
(1)Physiological functions of growth hormone.
1) Growth effect
Growth hormone stimulates cell division, especially in
  muscle and epiphyseal cartilage of long bones.
The result is muscular growth as well as linear growth.
GH also stimulates growth in several other tissues,
e.g.
skeletal muscle, heart, skin, connective tissue, liver,
kidney, pancreas, intestines, adrenals and
parathyroids.
Hypersecretion of GH leads to cause gigantism in
children and acromegaly in adult.
Hyposection of GH results in dwarfism during
childhood.
Effect of
hypophysectomy
on growth of the
immature rhesus
monkey.
 Both monkeys
were the same
size and weight 2
years previously,
when the one on
the left was
hypophysectomiz
ed.
Effect of growth hormone treatment for 4 days on
the proximal tibial epiphysis of the
hypophysectiomized rat.
Note that increased width of the unstained cartilage
plate in the tibia of the right, compared with the
control in the left.
    Growth Hormone Excess

• in childhood leads to GIGANTISM
If an acidophilic tumor
occur after adolescence –
that is , after the epiphyses
of the lone bones have fused
with shafts
– the person cannot grow
taller,
but the soft tissue can
continue to grow and the
bones can grow in thickness.
This condition is known as
acromegaly.
    Growth Hormone Excess

• in adulthood leads to ACROMEGALY
Receptor
mechanism of the
growth hormone
effect
GH
somatomedins (SM)
(also called
insulin-like growth
factor, IGF) in the
liver         growth
of bone and other
peripheral tissues.
2) Metabolic effects of GH
A, On Protein metabolism
Enhance amino acid transport to the interior of the
cells and increase RNA translation and nuclear
transcription of DNA to form mRNA, and so increase
rate of protein synthesis.
GH also reduces the breakdown of cell proteins by
decreasing catabolism of protein.
B, On fat metabolism
Cause release of fatty acids from adipose tissue and
then increasing the concentration of fatty acids.
Therefore, utilization of fat is used for providing
energy in preference to both carbohydrates and
proteins.
C. On glucose metabolism
Decreases cellular uptake of glucose and glucose
utilization,
leads to increase of the blood glucose concentration.
(2) Regulation of GH secretion
The plasma concentration of GH changes with age. 5 –
20 years old, 6ng/ml; 20 – 40 years old, 3ng/ml; 40 –
70 years old, 1.6ng/ml.
The change of GH concentration within one day.
1) Role of hypothalamus and feedback mechanism
                 -     Hypothalamus

                     GRH +        - SS
                -                         -
                         Pituitary

                                  GH
                         Liver



                             SM          Target tissues



   + increase the secretion; - inhibit the secretion
2) Other factors that affect the GH secretion
A, Starvation, especially with severe protein
deficiency
B, Hypoglycemia or low concentration of fatty acids
in the blood
C, Exercise
D, Excitement
E, Trauma
2. Prolactin (PRL)
(1)Physiological function of PRL
1) On breast: stimulate the development and milk
   secretion
In women, breasts development at puberty is
   stimulated by estrogen, progesterone, growth
   hormone, cortisol, insulin, thyroid hormones and
   prolactin.
During pregnancy, great growth of breast tissues
  occurs by stimulation of estrogen, progesterone and
  prolactin but estrogen and progesterone inhibit the
  secretion of milk.
Immediately after the baby is born, the sudden loss
of estrogen and progesterone secreted by the placenta
allows the lactogenic effect of PRL to assume its
nature milk promoting role, initiating milk secretion.
After birth of the baby, the level of PRL secretion
returns to the normal level before pregnancy but each
time the mother nurses her baby causes a 10 to 20 fold
surge in PRL secretion that lasts for about 1 hour.
Lactation is maintained for nursing period.
2) Effect on sexual organs
In women, PRL combined with PRL receptors in
granulosa cells stimulates production of LH receptors.
Through LH receptors, LH promotes ovulation and
then formation of corpus luteum. (permissive effect)
In male, PRL promotes growth of prostate glands and
seminal vesicle, enhancing the effect of LH on the
interstitial cells producing testosterone.
(2) Regulation of PRL secretion
1) Hypothalamic hormones and feedback
mechanism

          Hypothalamus: PIF              PRF
                                  -          +
                             +
           Anterior pituitary:   Prolactin


 + increase the secretion; - inhibit the secretion
2) Milk rejection reflex

                  Sucking, tactile stimulation


                  Afferent nerve (somatic nerve)

            Centers including spinal cord and hypothalamus


     PRF secretion                    Oxytocin secretion


    PRL secretion                Myoepithelial cells contraction
                                 of mammary glands


 Milk production increase                 Milk flows
PROLACTIN


   SECRETION
3. Synthesis and Release of Vasopressin (VP) and
   Oxytocin (OXT)
Cells in neurohypophysis do not synthesize hormones
  but act simply as supporting structure for nerve
  fibers.
Vasopressin (VP), also called ADH, and oxytocin (OXT) are
initially synthesized in the cell bodies of the supraoptic and
paraventricuar nuclei of hypothalamus
and are transported down to the nerve endings in the
neurohypophysis by hypothalamic hypophyseal tract.
When nerve impulses are transmitted downward along the
fibers from nuclei, the hormone is immediately released from
secretary granules in the nerve endings by exocytosis and is
absorbed into adjacent capillaries.
(1)Roles of ADH
1) Antidiuretic effect (refer to chapter 8)
2) Pressure effect. High concentration of ADH have a
   potent effect of constricting the arterioles
   everywhere in the body, raise the resistance blood
   flow and blood pressure
        Vasopressin
 Antidiuretic hormone V2-receptor:
        collecting duct
 Vasopressor hormone V1-receptor:
        vascular smooth muscle
(2) Role of Oxytocin (OXT)
1) Effect on mammary glands.
Cause the contraction of the myoepithelial cells that
  surround the outer walls of the alveoli of the
  mammary glands, press the milk from the alveoli to
  the duct and make it flow out --- milk ejection
Unconditioned and conditioned reflex
OXYTOCIN
2) Effect on uterus
OXT powerful stimulate the smooth muscle
contraction, especially that towards the end of
gestation.
It is believed that OXT is at least partially responsible
for causing birth of the baby
Section 3 Thyroid
  Gland
I. Functional
   Anatomy
largest endocrine
    glands in the body,
weighting about 20 –
   25g.
composed of large numbers of closed follicles filled
with colloid and lined with a layer of cuboidal
epithelioid cells.
The thyroid hormones are synthesized and secreted
by the epithelioid cells but stored in colloid.
 II. Production of Thyroid Hormones
 Iodide (I-) actively transported into the follicle and
  secreted into the colloid.
 Oxidized to iodine (Io).



H2O2
Hydrogen Peroxide
Iodine   attached to tyrosine within thyroglobulin
chain.
  –Attachment of 1 iodine produces monoiodotyrosine
  (MIT).
  –Attachment of 2 iodines produces diiodotyrosine (DIT).
Within the colloid, enzymes modify the structure of
MIT and DIT and couple them together.
When two DIT molecules are coupled together, a
molecule of tetraiodothyronine, T4, or thyroxine, is
produced.
The combination of one MIT with one DIT forms
triiodythyronine, T3.
Thyroid Hormone Synthesis:

                                          3’   3




                                          5’   5



                      DIT

  DIT + DIT = THYROXINE (T4)
        3, 5, 3’, 5’-TETRAIODOTHYRONINE

MIT + DIT = TRIIODOTHYRONINE (T3)
           3, 5, 3’-TRIIODOTHYRONINE
Note that within the colloid T4 and T3 are still
attached to thyroglobulin.

Upon stimulation by TSH,
                                            TSH
the cells of the follicle take
up a small volume of colloid
by pinocytosis,
hydrolyze the T3 and T4 from
the thyroglobulin, and
secrete the free hormones into
the blood.
III. Biological Actions of Thyroid
   Hormones

T3 and T4 (Almost all is deiodinated by one iodide ion,
   forming T3) bind with nuclear receptor,
activate and initiate genetic transcription. ---- mRNA
protein synthesis in cytoplasmic ribosomes ----
general increase in functional activity throughout the
   body.
1. On Metabolism
(1) Calorigenic action of thyroid hormones
Thyroid hormones increase O2 consumption of most tissues in
  the body, increasing heat production and BMR.
The mechanism of calorigenic effect of thyroid hormones may
  be:
A: Enhances Na+-K+ ATPase activity
B: Causes the cell membrane of most cells to become leaky to
   Na+ ions, which farther activates sodium pump and
   increases heat production.
(2) Effect on metabolism of protein, carbohydrate
   and fat
1) On Protein Metabolism.
Normally, T4 and T3 stimulates synthesis of proteins
  and enzymes, increasing anabolism of protein and
  causing positive balance of nitrogen.
In patient with hyperthyroidism,
catabolism of protein increases,
especially muscular protein, which
leads weigh-loss and muscle
weakness.
In patients with hypothyroidism, myxedema develops
because of deposition of mucoprotein binding with
positive ions and water molecules in the interstitial
spaces while protein synthesis decreases.


   Hypothyroidism
2) On carbohydrate metabolism
A: Increase absorption of glucose from the
gastrointestinal tract
E: Enhance glycogenolysis, and even enhanced
diabetogenic effect of glucagon, cortisol and growth
hormone.
C: Enhancement of glucose utilization of peripheral
tissues.
3) On fat metabolism
Thyroid hormones accelerate the oxidation of free
fatty acids by cells and increase the effect of
catecholamine on decomposition of fat.
Thyroid hormones not only promote synthesis of
cholesterol but also increase decomposition of
cholesterol by liver cells.
The net effect of T3 and T4 is to decrease plasma
cholesterol concentration because the rate of synthesis
is less than that of decomposition.
2. Effect of Thyroid Hormones on Growth and
Development
Thyroid hormone is essential for normal growth and
development especially skeletal growth and development.
Thyroid hormones stimulate formation of dendrites, axons,
myelin and neuroglia.
A child without a thyroid gland will suffer from critinism,
which is characterized by growth and mental retardation.
Without specific thyroid therapy within three months after
birth, the child with cretinism will remain mentally
deficient throughout life.
3. Effects of Thyroid Hormone on Nervous System
Thyroid hormones increase excitability of central
nervous system.

In hyperthyroidism, the patient
is likely to have extreme
nervousness, many
psychoneurotic tendencies
including anxiety complexes,
extreme worry and paranoia,
and muscle tremor.
                                  Hyperthyroidism
In addition, thyroid hormones can also stimulate the
sympathetic nervous system.
                              Hypothyroidism



   The hypothyroid
   individual is to have
   fatigue, extreme
   somnolence, poor
   memory and slow
   mentation.
4. Other Effects of Thyroid Hormone
(1)Effect on cardiovascular system
Thyroid hormones have a significant effect on cardiac
  output because of increase in heart rate and stroke
  volume, (may through enhance calcium release
  from sarcoplasmic reticulum).
(2) Effect on gastrointestinal tract
Thyroid hormones increase the appetite and food
intake by metabolic rate increased.
Thyroid hormones increase both the rate of secretion
of the digestive juices and the motility of the
gastrointestinal tract.
Lack of thyroid hormone can cause constipation.
IV Regulation of Thyroid Hormone Secretion
                              1. Hypothalamic
                              Pituitary Thyroid Axis
                               (1)Effect of TSH
                               1)Increase secretion of T4 and
                               T3 by proteolysis of
                               thyroglobulin
                               2) Increase synthesis of thyroid
                               hormones

through enhancement of ioidide trapping, ioidination of
tyrosine and coupling to form hormones
3) Stimulate thyroid gland to growth, increasing size and
number of thyroid cells
(2) TRH secreted by hypothalamus causes the anterior
pituitary to produce and release of TSH.


                             Cold and various
                             emotional reactions can
                             increase TRH secretion
                             through nervous system
                             and then
                             indirectly affect the
                             secretion of TSH and
                             thyroid hormones.
2. Feedback Mechanisms of Thyroid
Hormones
T3 and T4     inhibitory protein in anterior pituitary
reduces production and secretion of TSH,
decrease response of pituitary to TRH.
Because of the negative mechanism, the concentration
of free thyroid hormone in the blood can be
maintained within a normal range.
(Inhibitory Protein)
In the absence of sufficient dietary iodide the thyroid cannot
produce adequate amounts of T4 and T3.
The resulting lack of negative feedback inhibition causes
abnormally high level of the TSH secretion, which in turn
stimulate the abnormal growth of the thyroid (a goiter).
3. Autoregulation of Thyroid Hormone
Secretion
Without control of TSH, the thyroid gland can adapt
itself function to iodide uptake, which is the
autoregulation of thyroid gland.
In normal individuals, large doses of iodide act
directly on the thyroid gland to produce a mild and
transit inhibition of hormone synthesis.
When iodine is insufficient, the thyroid gland
increases formation of hormones.
In patients with hyperthyroidism,
iodides cause colloid to accumulate and the vascularity
of hyperplastic gland to decrease,
making iodide treatment considerable in preparing
patients for surgery.
4. Effect of Autonomic Nervous System on
Thyroid Activity
The thyroid gland is innervated by both sympathetic
nerve and parasympathetic nerve.
Electrical stimulation of sympathetic nerve increases
formation of thyroid hormones
while stimulation of cholinergic fibers (vagus nerve)
inhibits secretion of thyroid hormone.
Section 4 Adrenal Gland
The adrenal medulla secretes catecholamine
hormones.
The adrenal cortex secrete steroid hormones, which
participate in the regulation of mineral balance, energy
balance and reproductive function.
     Adrenal Cortex Anatomy

Divided into three regions:

       • zona glomerulosa
             - secretes aldosterone
       • zona fasciculata
             - secretes glucocorticoids
       • zona reticularis
             - secretes androgens
    Hormones of the Adrenal Cortex

• all adrenal cortex hormones are steroid
                                        CH2OH
                    HO

                                        C=O

                                           OH
                               HO




      O

                         O




          testosterone       cortisol


• not stored, synthesized as needed
I. Adrenal Cortical Hormones
The mineralocorticoids are secreted by zona
   glomerulosa,
regulates the concentration of the extracellular fluid.
Aldosterone is the principal mineralocorticoid.
The glucocorticoids are secreted by both zona
fasciculata and zona reticularis,
exhibiting an important effect on increasing blood
glucose concentration.
Cortisol is the principal glucocorticoid.




Small amounts of sex hormones are secreted by the
zona reticularis.
1. Biological Effects of Adrenocortical Hormones
(1) On metabolism
1) On carbohydrate metabolism.
A, Stimulation of gluconeogenesis (formation of
   carbohydrate from protein and other substances) by the
   liver through two pathways.
----Cortisol activates DNA transcription in the liver cell nuclei
    with formation of messenger RNAs that in turn lead to the
    array of enzymes required for gluconeogenesis.
----The other is cortisol causes mobilization of amino acids
    from extrahepatic tissues, mainly from muscle.
One of the effects of increased gluconeogenesis is a marked
  increase in glycogen storage in the liver cells.
B, Reduction of glucose utilization by the cells.
Cortisol decrease the rate of glucose utilization by the
cells everywhere in the body because of inhibition of
response of cells to insulin.
C, Elevate blood glucose concentration
2) On protein metabolism
A. Cortisol mobilizes amino acids from the
nonhepatic tissues and diminishes the tissue stores of
protein.
B. Cortisol decreases protein synthesis in body cells
except those of the liver and increases catabolism of
protein in many extrahepatic tissues especially in
muscle and lymphoid tissue.
C. In the presence of great excesses of cortisol, the
muscles become weak and the immunity functions of
lymphoid tissue decrease.
3) On fat metabolism
A. Cortisol promote mobilization of fatty acids from adipose
tissue which increases the concentration of free acids in the
plasma
B. Increases oxidation of fatty acids in the liver cells for
energy.
Cushing’ s
Syndrome
Many people with
excess cortisol
secretion develop a
peculiar type of
obesity, with excess
deposition of fat in
the chest and head
regions of the body,
giving a buffalo-like
torso and a rounded
face, a “moon-face”.
              Cushing’s Syndrome


“moon face”




     striae
 CORTISOL
   AND
FOODSTUFF
METABOLISM
4) Effects on water and electrolytes
Cortisol has a slight effect on enhancement of sodium
reabsorption and potassium excretion by distal tubules
and colleting ducts in kidney.
It increases the rate of renal blood flow and then
glomerular filtration rates, facilitating water excretion.
In patients with adrenal insufficiency, excretion of
water is so slow that there is a danger of water
intoxication and only glococorticoids can repair this
deficit.
(2) On blood cells
Cortisol increase the production of red cells and
platelets by stimulating bone marrow.
Cortisol decrease the number of lymphocytes and
eosinocytes because it causes atrophy of the all
lymphoid tissues and promotion of destruction of
lymphocytes and eosinocytes.
(3) On cardiovascular system
Glucocorticoids are necessary for maintenance of
  normal blood pressure. There are three mechanisms
  at least.
1) Cause permissive action, enhancing the response of
   vascular muscle to catecholamines.
2) Inhibit synthesis of prostaglandins that have
   vasodilator effect.
3) Reduces the permeability of capillaries, which is
   useful to maintenance of blood volume.
(4) Effect on stress.
Almost any type of stress, whether physical or
neurogenic, will cause increase in ACTH secretion,
and consequent cortisol secretion. This increase is
essential for survival.
(5) Other effects.
Glucocorticoids also have many other effects such as:
increase in production of HCl and pepsin,
promotion of synthesis of fetal surfactant.
Glucocorticoids have pharmacological effects
including anti-inflammatory, antiallergic and
antishock effect.
2. Regulation of Secretion of Adrenocortical Hormone
Hypothalamus –
  Anterior Pituitary
  – Adrenocortical
  Axis
(1) Action of ACTH:
    Cortisol secretion
    is almost entirely
    controlled by
    ACTH
    (adrenocorticotro
    pin hormone)
ACTH causes formation of
adrenocortical hormones by
increasing cAMP as a second
messenger and activates steps for
controlling adrenocortical
secretion.
Long-term stimulation of the
adrenal cortex by ACTH not only
increases secretory activity but also
causes hypertrophy and proliferation
of the adrenocorticol cells,
especially in the zona fasciculata
and zona reticularis, where cortisol
and androgens are secreted.
(2) CRH (corticotropin releasing
hormone)
A, Action of CRH
The action of CRH is to promote
synthesis and release of ACTH in
the cells of anterior pituitary gland.
B, Regulation of CRH secretion
CRH is secreted in irregular
bursts throughout the day and
plasma ACTH and cortisol tends
to rise and fall in response to these
bursts.
    Fluctuations in plasma ACTH and glucotorticoids
      throughout the day in a normal girl (age 16).

The
circadian
rhythm is
driven by
impulses
from the
supra-
chiasmatic
nuclei
Any type of stress can
lead to enhance
secretion of CRH
through afferent nerve
pathways on
hypothalamus.
Consequently, ACTH
secretion increases and
cortisol concentration
becomes very high in
the blood.
CRH secretion is
inhibited by cortisol via
a feedback mechanism
(3) Feedback
mechanism
Cortisol has direct
negative feedbacks on
the hypothalamus to
decrease formation of
CRH
High circulating
levels of cortisol
inhibit secretion and
formation of ACTH,
decreasing response
of anterior pituitary
gland to CRH.
High levels of ACTH
also inhibit CRH
secretion by a negative
feedback mechanism.
These feedbacks help
regulate the plasma
concentration of cortisol
toward a normal control
level.
Clinical treatment of cortisol (large does and long time)
always cause the atrophy of the adrenal gland. Please describe
the mechanism.
Section 5 Parathyroid Gland, Vitamin D and Parafollicular Cells


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