PARATHORMONE, CALCITONIN

AND
VITAMIN D
Physiological roles of Calcium
1. Bone and teeth formation
2. Muscle contraction
3. Blood clotting (conversion of prothrombin to thrombin)
4. Enzyme activation: some enzymes require calcium ion as a cofactor
for their activity (eg. Collagenase, lipase)
5. Nerve function: involved in transmission of nerve impulses,
activation of neurotransmitter release
6. Hormone secretion: role in exocytosis of granules
• Plasma calcium level regulated by 3 hormones parathormone
(PTH), calcitonin and calcitriol (active form of vitamin D)
• Calcium absorbed by facilitated diffusion from small intestine
• Vitamin D and PTH increase while calcitonin decreases tubular
reabsorption of calcium ion
Calcium preparations: Uses:
1. Calcium carbonate (40% Ca) 1. As dietary supplement: in
growing children, pregnant,
2. Calcium citrate (21% Ca)
lactating and menopausal
3. Calcium gluconate (9% Ca) women
4. Calcium lactate (13% Ca) 2. Osteoporosis (dec. bone density)
5. Calcium chloride (27% Ca) 3. Antacid (CaCO3​+2HCl→CaCl2​+CO2​
+H2​O)
Parathormone
• PTH is a single chain 84 amino acid polypeptide, MW 9500
• Secretion of PTH is regulated by plasma Ca2+ concentration through
a calcium-sensing receptor (CaSR), that is a G-protein coupled
receptor on the surface of parathyroid cells
• Fall in plasma Ca2+ induces PTH release and rise inhibits secretion by
decreasing cAMP in the parathyroid cells.
• The active form of vit. D calcitriol inhibits expression of PTH gene in
parathyroid cells reducing PTH production
• PTH increases plasma calcium levels by: reabsorption from bone, in
the distal tubule and by enhancing the formation of calcitriol in the
kidney by activating 1α-hydroxylase which promotes intestinal
absorption of calcium
Mechanism of action
• PTH receptor is GPCR activation increases cAMP formation and
intracellular Ca2+ in target cells.
• In bones, osteoblast are the target cells that respond to PTH
• In response to PTH, osteoblasts produce a factor called 'Receptor for
Activation of Nuclear Factor-κB Ligand' (RANKL)
• RANKL released by osteoblasts interacts with its receptor, RANK, on the
surface of osteoclast precursors transformation of osteoclast precursors
into mature osteoclasts resorbing bone, increases birth rate of bone
remodeling units
• Osteoblasts produce another protein OSTEOPROTEGERIN (OPG) as well,
which can bind RANKL and prevent it from combining with RANK to
activate osteoclasts. Thus, osteoblasts by producing RANKL and OPG
regulate bone resorption
Hypoparathyroidism
• When the parathyroid glands in your body don't produce enough
parathyroid hormone (PTH)
• The most common cause is damage to or removal of the parathyroid
glands during surgery, especially thyroid surgery.
• It can also result from autoimmune conditions, genetic factors, or other
medical issues.
• PTH is not used to treat hypoparathyroidism because plasma calcium
can be elevated and kept in the normal range more conveniently by vit
D therapy
• PTH has to be given parenterally, while vit D can be given orally
• Vit D is inexpensive.
• Recombinant human PTH (1–84 amino acid) has been produced
Hyperparathyroidism
• Due to parathyroid tumor
• Produces hypercalcemia, decalcification of bone (deformities and
fractures), muscle weakness
Cinacalcet
• Inhibits PTH secretion decrease plasma levels of PTH, calcium ions
• It is an orally active calcimimetic fluorinated compound
allosterically activates the calcium sensing receptor (CaSR) on
parathyroid cells and in other body tissues
Calcitonin
• It is hypocalcaemic hormone Synthetic salmon calcitonin is
• It is a 32 amino acid single chain polypeptide (MW used clinically more potent
3600) and longer acting due to slower
• Produced by parafollicular ‘C’ cells of thyroid gland. metabolism.
• Rise in plasma Ca2+ increases, while fall in plasma Human calcitonin has also been
Ca2+ decreases calcitonin release produced
• Actions of calcitonin are generally opposite to that Uses:
of PTH: 1. Hypercalcemic states
1. inhibits bone resorption by direct action on 2. Postmenopausal
osteoclasts osteoporosis
2. calcitonin inhibits proximal tubular reabsorption
of calcium and phosphate by direct action on the
kidney
Vitamin D

• These are antirachitic substances synthesized in the body

• D3 : cholecalciferol — synthesized in the skin under the influence of UV rays.
• D2 : calciferol—present in— yeasts, fungi, bread, milk
• Vit D2 and D3 are equally active and calcitriol (active form of D3 ) is more important physiologically
• 25-OH D3 is released in blood from the liver and binds loosely to a specific vit D binding globulin
• The final 1α-hydroxylation in kidney induced by calcium deficiency, PTH
Actions:
1. Calcitriol enhances absorption of calcium and phosphate by
increasing the synthesis of calcium channels and a carrier protein
for Ca2+ called ‘calcium binding protein’ (Ca BP) or Calbindin
2. Calcitriol enhances resorption of calcium and phosphate from
bone Like PTH, calcitriol induces RANKL in osteoblasts which may
then activate the osteoclasts.
3. Calcitriol enhances tubular reabsorption of calcium and phosphate
in the kidney
Vitamin D deficiency
• Plasma calcium and phosphate tend to fall in vit D deficiency as a
consequence, PTH is secreted and calcium is mobilized from bone in
order to restore plasma Ca2+ bones become soft producing rickets
Preparations
1. Calciferol
2. Cholecalciferol
3. Calcitriol
4. Alfacalcidol
5. Dihydrotachysterol
Uses
1. Prophylaxis and treatment of nutritional vit D deficiency: to
prevent or treat rickets in children and osteomalacia in adults
2. Postmenopausal osteoporosis: Vit D3 + calcium have been shown
to improve calcium balance in osteoporotic females and elderly
males.
3. Hypoparathyroidism: Calcitriol are more effective than vit D2 and
D3 because they act quickly
4. Fanconi syndrome (affects PCT leading to excretion of excessive phosphate
into the urine): Vit D can raise the lowered phosphate levels that
occur in this condition
Interactions
• Phenytoin and phenobarbitone (for epilepsy) reduce the
responsiveness of target tissues to calcitriol plasma level of
calcitriol is normal, but its effect on intestine and bone is diminished
• Cholestyramine (bile acid sequestrant used to lower cholesterol levels) and habitual
use of liquid paraffine (laxative )can reduce vit D absorption.