1. Parathyroid hormone(Parathormone) Lecture NO: 2nd MBBS
2/17/2019
Parathyroid hormone(Parathormone) Lecture NO: 2nd MBBS
Dr Muhammad Ramzan

2. Parathyroid hormone (PTH) – the definition
A protein hormone (84 AA.) from the Parathyroid gland that regulates the metabolism of :
Calcium and phosphorous in the body
It is also called as Parathormone (PTH)
– webster.com

3. Parathormone (PTH) – the background ↑ Ca and↓PO4 ions
PTH is important in bone remodeling via ongoing process of bone resorption and bone formation (Osteogenesis)
PTH elevates calcium level when it is low.
PTH excess causes bone/muscle pain and kidney stones
PTH deficiency produces muscle spasm; numbness in extremities, coagulation disorders and abnormal heart beats –

4. PTH – the target organs - 3 Bone, kidney and Intestine
2/17/2019
PTH – the target organs - 3 Bone, kidney and Intestine
Target organs are the ones with PTH receptors and include bones, Kidneys (CNS) and Intestine
No receptors for Intestinal mucosa and Osteoclasts
PTH acts via Osteoblasts and Osteocytes
Activates Vit. D in Kidneys through 1- α – hydroxylase to
Increase GIT Ca++ absorption
www. Labtestsonline.org

5. Target organs of PTH

6. Biosynthesis of PTH – As Pre Prohormone
2/17/2019
Biosynthesis of PTH – As Pre Prohormone
PTH is synthesized as a Pre Prohormone in the RER of the Chief cells with115 AAs
Pre-Pro PTH is cleaved by signal peptidase in RER to remove 25 AAs and is converted to Pro- PTH
Pro – PTH = 90 amino acids

7. Pro - PTH is transferred to Golgi 6 AAs are removed
2/17/2019
Pro - PTH is transferred to Golgi 6 AAs are removed
Pro - PTH is transferred to the Golgi Complex and 6 AAs are removed by Clipase for PTH = 84 AAs
PTH is packed/stored as secretary vesicles in Chief cells
Hormone Is released to the circulation in response to a proper physiological stimulus like:
Low Ca++ level in serum/ ECF

8. Biosynthesis of PTH

9. Regulation of PTH – 2 pathways
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Regulation of PTH – 2 pathways
PTH is regulated through negative feed back mechanism
Regulation is through 2 pathways
Direct and
Indirect

10. Regulation of PTH – Direct pathway No role of Calcitonin
It is the interaction B/W Ca++ level and PTH secretion
Low free calcium (Ions) in ECF is sensed by the Calcium sensory receptors - Integral membrane proteins
It ↑ the secretion of PTH that elevates Ca++ level by its action on the target organs (bones and Kidneys)
There is no role of Calcitonin
colostate.com

11. Regulation of PTH – Direct pathway

12. PTH Regulation – Indirect pathway ↑ Ca, PTH and Calcitonin
It is interaction B/w high serum Ca++, PTH and Calcitonin
High serum Ca++ Induces the following changes
1. ↓Transcription of mRNA for PTH (synthesis)
2. Auto degradation of the preformed PTH secretary granules
Secretion of Calcitonin reduces the Ca++ by promoting its renal excretion and bone formation

13. Homeostasis of blood calcium Role of Calcitonin and PTH

14. PTH - Mechanism of Action Activation of GPCR – PTHR1
PTH is a protein hormone and its action is like the similar ones
PTH binds to the Extracellular domain of the PTHR1 on the membranes of bones to produce some changes
It activates the intracellular α - subunit of the G protein to produce α – GTP in exchange for α- GDP

15. PTH - Mechanism of action ( PTHR1) activation of adnylate cyclase
2/17/2019
PTH - Mechanism of action ( PTHR1) activation of adnylate cyclase
α- GTP activates the membranous Adenylate Cyclase of the target cells that convert ATP to cAMP
cAMP is the 2nd messenger
cAMP activates the Protein kinas A, that Phosphorylates the specific intracellular enzymes/ proteins
to execute the hormonal effects - ↑ serum Calcium

16. Mechanism of Action of PTH – PTHR1

17. PTH – Alternate mechanism activation of Phospholipase C
An alternate mechanism of action of PTH
Activated α GTP also stimulates Phospholipase C
It converts membranous Phospholipid, PIP2 into:
IP3 and DAG as 2nd messengers
Both act on the bone, kidneys and intestine to increase extracellular Calcium

18. PTH mechanism of action – Dual pathways

19. Metabolic actions of PTH
PTH acts to maintain serum/ECF Calcium between
mg/dl and Po4 B/W mg/dl
PTH has significant metabolic actions on :
Bones, Kidneys and Intestine

20. Metabolic role of PTH – the target organs

21. PTH - Metabolic actions on bone
2/17/2019
PTH - Metabolic actions on bone
Bone is a large reservoir of Calcium
PTH enhances the release of Ca and Po4 from the bone by Osteolysis via Osteoclasts - a normal process
Osteolysis is also supported by the :
1. Membranous Calcium pump activated by PTH
2. Elevated Phosphatases around Osteoclasts

22. Activated Osteoclasts

23. Membranous Calcium pump – How it works
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Membranous Calcium pump – How it works
Calcium pump causes rapid removal of calcium phosphate from the sites near these cells (Osteoclasts)
Calcium phosphate salts are transported to ECF as:
It alters the permeability of Osteocytes to calcium

24. Metabolic action on Kidneys ↑ Cal. Resorption and Po4 excretion
PTH promotes renal excretion of Phosphates to decrease its plasma level and
Enhances active resorption of Ca and Mg from the distal tubules and ascending loop of Henley
This increases Calcium phosphate ratio (3:11) and more free Ca++ ions in circulation

25. Metabolic actions on Kidneys cont. Activation of Vit.D for GIT
PTH promote activation of Vitamin D to 1-25 Dihydroxy Cholecalceferol in kidneys via 1- α- hydroxylase
Vita. D promotes calcium absorption from GIT
It is facilitated by Calbindin (Ca binding protein)
No PTH receptors are present on Intestinal mucosa
PTH has no significant effect on Po4 absorption by GIT

26. PTH - secretion abnormalities
Parathormone may be secreted in excess or there may be deficiency of PTH secretion
Both abnormalities lead to significant clinical conditions

27. PTH excess - hyperparathyroidism
Excessive PTH secretion is classified as :
Primary and secondary
Primary one is the result of diseases of parathyroid and is due to tumour of the gland
Results in hypercalcemia, kidney stones and osteoporosis

28. Hyperparathyroidism - Secondary
Secondary one is due to causes out side the parathyroid
Common cause is the:
1. Renal disease/ failure as it is unable to reabsorb Calcium and there is fall in blood Ca.
2. Malnutrition for Calcium and Vit. D produces :
Decalcification of bone leading to rubber bones,
pathological fractures and cyst formation

29. PTH deficiency – Hyoparathyroidism
It refers to the condition when PTH is produced less than the body requirements. Caused by:
Inborn error of metabolism and autoimmune disorders.
Hyoparathyroidism results in :
1. Reduction of Serum calcium
2. Defects in muscle contraction and
3. Tetany

30. Parathormone
Calcitonin
Site of synthesis
RER of chief cell of parathyroid gland – A protein hormone
RER of Para follicular cells of thyroid gland – A protein hormone
Structure
A Prohormone with 115 AAs – processed in Golgi to 84 AAs
A Prohormone with 115 / 142 as processed in Golgi to 32 AAs.
Target organs
3 – bone, kidney and intestinal mucosa no receptors for Osteoclasts and intestinal mucosa
2 – bones and renal tubular cells – no receptors at Osteoclasts, but present at other bone cells and kidneys
Nature of Action
Increases the calcium from Low to High via osteoclastic activity
Decreases serum Ca level when high Via osteoblastic activity and inhibiting PTH
Regulation of secretion
Direct – interaction B/W low calcium and parathyroid gland
Indirect – interaction B/W high calcium PTH and Calcitonin
Direct – interaction B/W high serum and ECF and Calcitonin
Indirect – interaction B/W low Ca level and Calcitonin and PTH
Stimulates PTH secretion to increase Ca level in serum and ECF
Metabolic Actions
Via 2nd messenger (cAMP)
Maintains the serum concentration of Ca B/W 9.5 – 10.5mg /dl and PO 3.5 – 4.5 mg/dl
Maintains the Ca level in serum and ECF by reducing the Osteoclastic activity when high
Secretion Abnormalities
Excess – hyperparathyroidism osteoporosis, pathological fracture Deficiency low Ca level tetany and defects in muscle contraction
Not significant Excess or Deficiency – used in the treatment of post menopausal osteoporosis and malignancies