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Parathyroid Hormone

Parathyroid Hormone

    Two pairs of small oval shaped parathyroid glands located on the posterior of thyroid gland

    Primarily concerned with Ca2+ and PO43homeostasis through its secretion

(parathormone)

 

    Parathormone (PTH):

    Secreted by Chief cells of the parathyroid gland

  Most important regulator of calcium and phosphorus concentration in extracellular fluid

    Chemistry:

    Linear polypeptide hormone with 84 amino acids

  Alanine is present at N-terminal

  Glutamine is present at C-terminal

    Aminoacid sequence 1 to 34 is important for its biological activity

  Possesses receptor binding properties

    Methionine is necessary for calcium mobilizing effects

Biosynthesis:

    PTH is originally synthesized as a pro-hormone in the chief cells

  Initially 115 aminoacid based pre-pro-parathormone is formed in polysomes

  Pre-pro-PTH is hydrolysed  to pro-PTH with 90 AA

    25 aminoacids are removed during hydrolysis

  Finally further removal of hexapeptide converts pro-

PTH to active parathormone

    Stored in secretory vesicles of golgi bodies

    Release:

  Regulated by –ve feedback regulation of serum Ca2+

  Increase cAMP and low Ca2+ stimulates its release

Mechanism of Action:

    Act by binding specific receptors on plasma membrane of bone, kidney and intestinal cells

    Activate cAMP through adenylyl cyclase

    cAMP 

  activates protein kinases

  increase intracellular Ca2+ concentration

    Act as another second messenger

    Both cAMP and increased Ca2+ activates intracellular proteins and generate its response Physiological functions:

    The prime function of PTH is to elevate serum calcium levels by acting on bones, kidneys and intestine independently

i) Action on bones:

    It causes decalcification or demineralization of bones

  Very significant role in Ca2+ homeostasis

    It increase cAMP in

  Osteoclasts

  Osteoblasts

  Osteocytes 

    Here it activates protein kinase enzymes that:

  Stimulate differentiation and maturation of osteoclasts

  Increase resorption of bones

    Enhance Ca2+ and PO43- mobilization from bones

    Increased overall serum Calcium level

ii) Action on Kidneys:

    Increase Ca2+ re-absorption from kidney tubules

    Stimulates α-1-hydroxylase in mitochondria of

PCT

Converts 25-hydroxy cholcalciferol to 1,25-dihydroxy cholcalciferol

    Increase the intestinal and renal absorption of Ca2+

    Increase excretion of PO43-, K+ and HCO3- by decreasing their re-absorption

iii) Action on intestine:

    Indirectly increase the Ca2+ absorption by promoting the synthesis of calcitriol Overall action of PTH and calcitonin are opposite to each other in regulating blood Ca2+

 

Disorders of Parathyroid hormones:

    Hyperactivity of parathormone may induce:

Hypercalcemia, that may lead to 

    kidney stones

    High blood pressure

Osteoporosis due to over demineralization of bones

    General symptoms of hyperparathyroidism are:

  Muscle weakness, fatigue, depression and aches & pains in joints and bones

  In Severe cases increased thirst and urination is also observed

    Hypoparathyroidism increase the risk of

  Addison’s disease, cataracts, Parkinson’s disease etc.


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