This presentations contains information about parathyroid hormone. Also explains hormones involved in regulation of calcium homeostasis.

1. Parathyroid Hormone
Dr. Rupali A. Patil
Associate Professor, Pharmacology Department
GES’s Sir Dr. M. S. Gosavi College of Pharmaceutical Education & Research,
Nashik

2. Parathyroid Gland
 Human beings : 04 parathyroid glands,
situated on the posterior surface of
upper & lower poles of thyroid gland.
 Very small in size, dark brown color.
 Dimensions:
6 mm long, 3 mm wide & 2 mm thick,.

3.  Made up of chief cells and oxyphil cells.
1. Chief cells:
 Secrete parathormone.
2. Oxyphil cells
 Degenerated chief cells & their function
is unknown.
 May secrete parathormone during
pathological condition called parathyroid
adenoma.
Histology

4.  The adult human body contains 1 Kg of calcium
 Calcium is very essential for many activities in the body such as:
1. Bone and teeth formation
2. Neuronal activity
3. Skeletal muscle activity
4. Cardiac activity
5. Smooth muscle activity
6. Secretory activity of the glands
7. Cell division and growth
8. Coagulation of blood
Calcium homeostasis
99% stable in
mineralized
bone
1% exchangeable
in bone fluid

5. Its concentration is about 10mg/dl
1. Ionized : 50%
2. Bound to protein : 40%
3. Complex & diffusible form : 10%
Plasma calcium:

6. Composition of bone tissue
1. Organic matrix (formed mainly of collagen)
2. Crystalline salts (mainly hydroxyapatite crystals &
calcium phosphate)
3. Bone cells
A. Osteoblast
B. Osteocyte
C. Osteoclasts
Bone

7. ▪Bone matrix
proteins
▪Alkaline
phosphatase
Bone
forming
cells
Secrete ▪ H+ that
dissolve
▪Acid protease
that dissolve
collagen
Bone
hydroxyapatite eating
cells
Secrete
Phosphate
ester phosphate
Ca
phosphate

8. Parathormone
 Secreted by Chief cells of parathyroid gland
 Protein in nature, 84 amino acids.
 Molecular weight : 9,500
 Half-life and Plasma Level
 Parathormone has a half-life of 10 minutes.
 Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
 Essential for the maintenance of blood Ca level within a very
narrow critical level.
 Calcium : an important inorganic ion for many physiological
functions.

9.  Synthesis
 Precursor : pre-pro-PTH : 115 amino acids.
 PRE-PRO-PTH enters the endoplasmic reticulum of chief cells of
parathyroid glands
 Converted into a prohormone called pro-PTH (96 amino acids).
 Pro-PTH enters the Golgi apparatus, where it is converted into PTH.
 Metabolism
 60 – 70 % of PTH is degraded by Kupffer cells of liver, by means of
proteolysis.
 Degradation of about 20% to 30% PTH occurs in kidneys & to a lesser
extent in other organs.

10.  Actions Of Parathormone on Blood Calcium Level
 Primary action of PTH is to maintain the blood calcium level
within the critical range of 9 to 11 mg/dL.
 PTH maintains blood calcium level by:
1. Resorption of Ca from Bones
2. Reabsorption Ca from the renal tubules (Kidney)
3. Absorption of Ca from Gastrointestinal tract.

11.  On Bones
 Parathormone enhances the resorption of calcium from the bones
by acting on osteoblasts and osteoclasts of the bone.
 Resorption of calcium from bones occurs in two phases:
1. Rapid phase
2. Slow phase

12.  Rapid phase
 Rapid phase occurs within minutes after the release of PTH from
parathyroid glands.
 Immediately after reaching the bone, PTH gets attached with the
receptors on the cell membrane of osteoblasts and osteocytes.
 The hormone-receptor complex increases the permeability of
membranes of these cells for calcium ions.
 It accelerates the calcium pump mechanism, so that calcium ions
move out of these bone cells & enter the blood at a faster rate.

13.  Slow phase
 Slow phase of calcium resorption from bone is due to the activation
of osteoclasts by PTH.
 When osteoclasts are activated, some substances such as proteolytic
enzymes, citric acid & lactic acid are released from lysosomes of
these cells.
 All these substances digest or dissolve the organic matrix of the
bone, releasing the calcium ions.
 The calcium ions slowly enter the blood.
PTH increases calcium resorption from bone by stimulating the proliferation of
osteoclasts also.

14.  On Kidney
 PTH increases the reabsorption of calcium from the renal tubules
along with magnesium ions an hydrogen ions.
 It increases calcium reabsorption mainly from distal convoluted
tubule and proximal part of collecting duct.
 PTH also increases the formation of 1,25- di-hydroxycholecalciferol
(activated form of vitamin D) from 25-hydroxycholecalciferol in
kidneys.

15. Ca++ reabsorption
Phosphate reabsorption
Ca++ absorptionECF Ca++
ECF PO4
3-

17.  On Gastrointestinal Tract
 Increases the absorption of Ca ions from the GI tract indirectly.
 Increases the formation of 1,25- dihydroxycholecalciferol in
the kidneys.
 This vitamin, in turn increases the absorption of Ca from GI tract.
 Activated vitamin D is very essential for the absorption of Ca from the GI
tract & PTH is essential for the formation of activated vitamin D.

18.  Role of PTH in the activation of vitamin D
 Vitamin D is very essential for Ca absorption from the GI tract.
 Vitamin D itself is not an active substance.
 Instead, vitamin D has to be converted into 1, 25-
dihydroxycholecalciferol in the liver and kidney in the presence of PTH.
 1,25-dihydroxycholecalciferol is the active product

20.  Activation of vitamin D
 There are various forms of vitamin D: most important one is vitamin D3.
 Also known as cholecalciferol.
 Vitamin D3 is synthesized in the skin from 7- dehydrocholesterol, by
the action of ultraviolet rays from the sunlight.
 Also obtained from dietary sources.

21.  The activation of vitamin D3 occurs in two steps:
 First step
 Cholecalciferol (vitamin D3) is converted into 25-hydroxycholecalciferol in
the liver
 This process is limited & is inhibited by 25-hydroxycholecalciferol
itself by feedback mechanism
 Second step
 25-hydroxycholecalciferol is converted into 1,25-dihydroxycholecalciferol
(calcitriol) in kidney.
 It is the active form of vitamin D3.
 This step needs the presence of PTH

22.  Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol
 When blood calcium level increases, it inhibits the formation of 1,25-
dihydroxycholecalciferol. The mechanism involved in the inhibition of
the formation of 1, 25-dihydroxycholecalciferol is as follows:
1. Increase in calcium ion concentration directly suppresses conversion
of 25- hydroxycholecalciferol into 1,25-dihydroxy cholecalciferol.
2. Increase in calcium ion concentration decreases the PTH secretion,
which in turn suppresses the conversion of 25-hydroxycholecalciferol into
1, 25-dihydroxycholecalciferol

23.  Actions of 1, 25-Dihydroxycholecalciferol
 It increases the absorption of calcium from the intestine, by increasing
the formation of calcium binding proteins in the intestinal epithelial
cells.
 These proteins act as carrier proteins for facilitated diffusion, by which the
calcium ions are transported.
 The proteins remain in the cells for several weeks after 1,25-
dihydroxycholecalciferol has been removed from the body, thus causing
a prolonged effect on calcium absorption
 It increases the synthesis of calcium-induced ATPase in the intestinal
epithelium
 It increases the synthesis of alkaline phosphatase in the intestinal
epithelium
 It increases the absorption of phosphate from intestine along with calcium

25. Regulation Of Parathormone Secretion
 Blood level of calcium is the main factor regulating the secretion of
PTH.
 Blood phosphate level also regulates PTH secretion.

26.  Blood Level of Calcium
 Parathormone secretion is inversely proportional to
blood calcium level.
 Increase in blood calcium level decreasesPTH secretion.
 Conditions when PTH secretion decreases are:
1. Excess quantities of calcium in the diet
2. Increased vitamin D in the diet
3. Increased resorption of calcium from the bones, caused by some other
factors such as bone diseases.
 Decrease in calcium ion concentration of blood increases PTH
secretion, as in the case of rickets, pregnancy and in lactation

28.  Blood Level of Phosphate
 PTH secretion is directly proportional to blood phosphate level.
 Whenever the blood level of phosphate increases it combines with
ionized calcium to form calcium hydrogen phosphate.
 This decreases ionized calcium level in blood which stimulates PTH
secretion

30. Source: Skin
25-hydroxy-
cholecalcife
rol
1, 25-dihydroxy cholecalciferol
ECF Ca++
ECF PO43-

31. 3. Calcitonin
Source: parafollicular cells
Actions:
1. On Bone (inhibits activity of osteoclast)
2. On kidney
ECF Ca++
ECF PO4
3-
Ca++
PO4

32. • PTH: stimulates osteoclasts, inhibits osteoblasts
– Calcium released
• Hypoparathyroidism
– If parathyroid removed:
• Decreased calcium levels
• tetany and death without HRT
• Hyperparathyroidism:
– Bone softening, fragility, deformity
– Renal calculi formation

33. Summary

34. Thank you