TSM93: calcium homeostasis 2 28/11/08
Learning Outcomes
Describe the hormonal regulation of plasma calcium levels
· There are three key hormones in calcium homeostasis:
o Parathyroid hormone (PTH) – increases plasma calcium (hypercalcaemic)
o 1,25-DHCC (calcitrol) – increases plasma calcium
o Calcitonin – reduces plasma calcium (hypocalcaemic)
· Parathyroid hormone is a peptide hormone produced by chief cells of the parathyroid glands
o Low plasma calcium levels stimulate its secretion – very sensitive
o Acts directly on bone to stimulate osteoclasts and hence bone resorption
§ Also inhibits osteoblastic collagen synthesis to prevent bone formation
o Acts directly on the kidneys to stimulate calcium reabsorption in the distal tubule
§ Also stimulates production of 1,25-DHCC (see below)
o Has no direct effect on the intestines
· 1,25-DHCC is a metabolite of vitamin D3 formed by hydroxylation in the liver and kidney
o Acts directly on the intestines to promote production of CaBP stimulating calcium absorption
§ Increased intracellular calcium binding buffers calcium levels increasing the gradient
o Has minor effects in increasing renal reabsorption and PTH stimulation of bone resorption
· Calcitonin is a peptide hormone produced by the parafollicular cells of the thyroid gland
o High plasma calcium levels stimulate its secretion; not very significant in daily calcium balance
o Acts directly on bone to inhibit osteoclasts and hence prevent bone resorption
o Has minor effects in decreasing renal reabsorption but no effect on the intestines
Describe the role of Vitamin D in calcium homeostasis
· Vitamin D is structurally similar to a steroid hormone and can be synthesised from cholesterol
o UV light on the skin is crucial in the synthesis of vitamin D from cholesterol
o Main direct dietary source is dairy products
o Active human form is vitamin D3
· The calcium homeostasis hormone 1,25-DHCC is a di-hydroxyl derivative of vitamin D3
o The liver hydroxylates C25 (making 25-HCC – predominant circulating form)
o The kidneys hydroxylate C1 (via 1-α-hydroxylase – stimulated by PTH)