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 PO₄^3- 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 PO₄^3-, 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.