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PARATHYROID HORMONE by mikesanye

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									PARATHYROID HORMONE
DR AMINA TARIQ
BIOCHEMISTRY
PARATHYROID GLANDS
 They are the smallest endocrine glands in the
  body.
 They are usually four in number

 And are embedded in the substance of the
  thyroid gland.
 The gland consists of two types of cells: Chief
  cells and Oxyphil cells.
 Chief cells are the secretory cells and are
  concerned with the secretion of PTH.
HISTORY

   The parathyroid glands were first discovered in
    the Indian Rhinoceros by Richard Owen in 1850.

   The glands were first discovered in humans by
    Ivar Viktor Sandström (1852-1889), a Swedish
    medical student, in 1880.

   It is the last major organ to be recognized in
    humans so far.
PARATHYROID HORMONE
BIOSYNTHESIS:
 It is a linear polypeptide.

 Consists of 84 amino acids.

 PTH is first produced as pre-pro PTH having 115
  amino acids.
 Then 15 AA are split off and Pre-PTH with 90 AA
  is formed.
 Then in the Golgi 6 more AA are removed and
  PTH is formed with 84 AA.
   PTH AA 1- 34 has full biologic activity, and the
    region 25-34 is responsible for receptor binding.
SECRETION:
 Secretion of PTH is regulated by plasma ionized
  calcium levels.
 An acute decrease of Ca results in a marked
  increase in the PTH mRNA.
 This is followed by increase synthesis and
  secretion of PTH.
MECHANISM OF ACTION:
 PTH binds to specific receptor on the plasma
  membrane of bone cells and renal tubule cells.
 It activates adenyl cyclase to form cAMP.

 cAMP acts as a second messenger and activates
  cAMP-dependent protein kinases.
 These kinases phosphorylate and modulate the
  activities of specific proteins in the bone cells and
  kidney cells.
   PTH may also act through Phosphatidylinositol
    pathway.
METABOLIC ROLE OF PTH:
 Increase in serum Ca concentration.

 Decrease in serum inorganic PO4.

 Increased urinary PO4.

 Removes calcium from the bones especially if
  dietary intake of Ca is inadequate.
 Activates vit D in renal tissue by increasing the
  rate of conversion of 25-OH cholecalciferol to 1,25
  di-OH cholecalciferol by stimulating I α-
  hydroxylase.
 Increase PTH also increases Mg urinary
  excretion.
ACTION ON KIDNEYS:
 It decreases the trans membrane transport and
  reabsorption of filtered Pi in both proximal and
  distal tubules.
 And this leads to increase urinary excretion of Pi
  (Phosphaturic effect).
 When the levels of Pi falls in serum, it causes the
  mobilization of PO4 from bones, which also
  mobilizes Ca along with it (Hypercalcemia).
 PTH also decreases the trans membrane
  transport of K+ and HCO+3 to decrease their
  reabsorption by renal tubules.
 It increases the trans membrane transport and
  reabsorption of filtered Ca2+ in distal tubules.
 And this leads to decrease urinary excretion of
  Ca2+ .
ACTION ON BONES:
 PTH binds to specific receptors present on
  membranes of osteoclasts, osteoblasts and
  osteocytes.
 Differentiation and maturation of precursor cells
  of osteoclasts.
 Osteoclastic activity is increased.

 Alkaline phosphatase activity varies according to
  the concentration of PTH.
 At low levels of PTH the alkaline phosphatase
  and osteoblastic activity is raise.
 But high physiological levels decrease the
  calcium retaining properties of osteoblasts.
 ACTION ON INTESTINAL MUCOSA:
 Action is not direct but through Vit D, which
  increases the absorption of Ca2+ and PO4.
 Even the slightest decrease in the Ca conc in the
  ECF can increase the rate of secretion of PTH.
 PTH glands become greatly enlarged in Rickets.

 In Pregnancy.

 In Lactation.
 Conversely conditions that increase the levels of
  Ca ions will decrease the secretion of PTH.
 Excess quantity of Ca in the diet.

 Increased vit D in the diet.

 Bone resorption in bone diseases
PARATHORMONE-RELATED PEPTIDE
 PTHrP is also called Humoral Hypercalcaemic
  factor of malignancy.
 Produced by a number of tumors espacially
  squamous cell ca of lungs, esophagus, cervix.
 Renal, pancreatic, breast.

 It can bind to the same receptor as PTH and can
  mimic the action of PTH.
 Target tissues are bones and kidneys.
 Produces hypercalcemia, hypophosphatemia.
Clinical Importance:
 Serum levels of PTHrP are low or absent in
  normal healthy persons and in patients with
  primary hyperparathyroidism.
 But it is high in majority of patients in
  malignancy.
 Becoming an important diagnostic tool in
  evaluation of hypercalcaemia.
CALCITONIN
 Calcitonin is a polypeptide of 32 amino acids. The
  thyroid cells in which it is synthesized have
  receptors that bind calcium ions (Ca2+)
  circulating in the blood.
 These cells monitor the level of circulating Ca2+.
  A rise in its level stimulates the cells to release
  calcitonin.
 As the level of calcium in the blood rises, the
  amount of calcitonin secreted by the C cells of the
  thyroid increases.
 Calcitonin stimulates osteoblasts to form bone
  taking calcium out of the circulation.
 At the same time, calcitonin inhibits the
  mobilization of bone (and calcium) by
  osteoclasts. The end result is a decrease in the
  level of calcium in the blood thus helping to
  maintain proper blood calcium levels.
   Because it promotes the transfer of Ca2+ to bones,
    calcitonin is used as a possible treatment for
    osteoporosis.
PARATHYROID HORMONE
   A decrease in the normal levels of calcium in the
    blood causes the chief cells of the parathyroid
    gland to secrete more parathyroid hormone
    which stimulates osteoclasts to mobilize bone
    resulting in an increase in the level of calcium in
    the blood. Parathyroid hormone also increases
    Ca ion reabsorption in the kidney and decreases
    the reabsorption of phosphate ions.
 Resorption: the process of breaking down and
  assimilating (Ca2+ mobilization)
 Reabsorption: the process of re-absorbing
  (absorbing again).
LEARNING RESOURCES

 Harper Biochemistry
 Mushtaqs Biochemistry – vol-II

 Teacher Notes

								
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