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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