1. Endocrine Regulation of Calcium and Phosphate Metabolism
Huiping Wang (王会平), PhD
Department of Physiology
Rm C516, Block C, Research Building, School of Medicine
Tel:

2. Outline Hormonal Regulation of [Ca2+] Action of PTH
Action of vitamin D(1,25- (OH)2-D3)
Action of calcitonin

4. Endocrine Regulation of Calcium and Phosphate Metabolism
Hormonal control:
PTH, vitamin D(1,25- (OH)2-D3), calcitonin
Major regulatory organs:
intestine, bone, kidneys

5. Vitamin D
Vitamin D, after its activation to the hormone 　1,25(OH)2D, is one of the major regulators of Ca & Pi metabolism
Sources of vitamin D:
produced in the skin by UV radiation (D3)
ingested in the diet (D3 rich in fish, liver, milk)
Vitamin D is not a “classic hormone” because it is not produced by an endocrine gland. However, its metabolite acts as a hormone by the mechanism similar to that of thyroid and steroid hormones

6. Formation of Active Vitamin D
Sunlight ( nm) stimulates skin cell to produce previtamin D3 which is then converted to vitamin D3
Over exposure to sunlight converts previtamin D3 to inactive products
Vitamin D has very little intrinsic biological activity and must undergo successive hydroxylations in order to act as a hormone
In liver, it is hydroxylated to 25-OH-D which is transported to kidney to form 1,25-(OH)2-D or 24,25-(OH)2-D
1,25-(OH)2-D is the most potent vitamin D metabolite

7. Actions of 1,25-(OH)2-D3 Acts through nuclear receptors Intestine Bone
increases Ca absorption
stimulates phosphate absorption
Bone
stimulates Ca and Pi resorption
provides Ca and Pi from old bone to mineralize new bone
kidney
Enhances Ca and Pi reabsorption of renal tubule

8. Rickets
Deficiency of vitamin D causes inadequate mineralization of new bone matrix (lowered ratio of mineral/organic matrix)
Caused by deficiency of vitamin D activity (dietary deficiency, insufficient sun exposure, liver/kidney diseases)
Symptoms: decreased mechanical strength and distortion especially in the long bones of legs.

9. Parathyroid Glands 4 glands located behind the thyroid
each gland weighs mg
main cell type:
chief cells
Parathyroid Hormone

10. Parathyroid Hormone (PTH)
Polypeptide

11. PTH Actions Major target organs Overall effect bone
 Bone resorption by stimulating osteoclasts and osteocytes and inhibiting osteoblasts
kidney
Reabsorption of Ca++ and excretion of phosphate
intestinal tract (indirect effect)
Absorption of calcium from the small intestine
Overall effect
increase plasma [Ca2+]
decrease plasma [Pi]

12. Factors Affecting PTH Secretion
Ca and PTH form a negative feedback pair
1,25-(OH)2-D and PTH form negative feedback loop

13. damage to blood supply during thyroidectomy
Hypocalcemia
damage to blood supply during thyroidectomy

14. Calcitonin Parafollicular or C cells Peptide Action Regulation: [Ca2+]
Plasma [Ca2+]
Bone
by inhibiting osteoclasts (for bone resorption) & stimulating calcium uptake by bones
By inhibiting synthesis and activity of osteoclasts
Kidney
Regulation: [Ca2+]
It plays no role in normal day-to-day regulation of plasma calcium regulation in humans
Calcitonin is used in
acute treatment of hypercalcemia
alternative of estrogen for treating osteoporosis in women

15. Hormonal Regulation of [Ca2+]

16. QUIZ
A patient with parathyroid deficiency 10 days after inadvertent damage to the parathyroid glands during thyroid surgery would probably have
A. low plasma phosphate and Ca2+ levels and tetany B. low plasma phosphate and Ca2+ levels and tetanus C. a low plasma Ca2+ level, increased muscular excitability, and a characteristic spasm of the muscles of the upper extremity (Trousseau’s sign) D. high plasma phosphate and Ca2+ levels and bone demineralization E. increased muscular excitability, a high plasma Ca2+ level, and bone demineralization

17. QUIZ
A patient with parathyroid deficiency 10 days after inadvertent damage to the parathyroid glands during thyroid surgery would probably have
A. low plasma phosphate and Ca2+ levels and tetany B. low plasma phosphate and Ca2+ levels and tetanus C. a low plasma Ca2+ level, increased muscular excitability, and a characteristic spasm of the muscles of the upper extremity (Trousseau’s sign) D. high plasma phosphate and Ca2+ levels and bone demineralization E. increased muscular excitability, a high plasma Ca2+ level, and bone demineralization

18. QUIZ
Which of the following is not involved in regulating plasma Ca2+ levels?
A. Kidneys B. Skin C. Liver D. Lungs E. Intestine

19. QUIZ
Which of the following is not involved in regulating plasma Ca2+ levels?
A. Kidneys B. Skin C. Liver D. Lungs E. Intestine

20. Summary Hormonal Regulation of [Ca2+] PTH: [Ca2+]
Vitamin D(1,25- (OH)2-D3): [Ca2+]
Calcitonin: [Ca2+]