Osteoclasts parathormone effect

The polypeptide parathormone is released from the parathyroid glands when plasma Ca + level falls. It stimulates osteoclasts to increase bone resorption in the kidneys, it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of calcium to precipitate as bone mineral decreases. By stimulating the formation of vit D hormone, parathormone has an indirect effect on the enteral uptake of Ca + and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that unlike parathormone, is effective orally. 

Parathormone also increases DNA, RNA, and protein synthesis in osteoclasts, but decreases such synthetic processes in osteoblasts. These findings are in keeping with the role of the hormone in bone resorption. The intramitochondrial calcium granules in bone cells are also increased after the administration of parathormone. Whether this effect is related to calcium release remains to be shown. The exact molecular sequence that leads to calcium resorption in bone is not known. But it has been established in experiments using bone calvaria and isolated bone cells that parathormone elicits the formation of a second messenger namely, cyclic AMP (see chapter on hormones) through the stimulation of adenylcyclase. 

Postmenopausal bone loss is effectively inhibited by prophylactic administration of estrogen (Recker et al, 1977), but estrogen administration to osteoporotic patients (the conventional treatment) fails to restore lost bone. Estrogen appears to act primarily by putting a brake on bone resorption, i.e., it inhibits the action of parathyroid hormone, the primary stimulus to osteoclastic bone resorption. The mechanism of this inhibition is unknown receptors for estrogen have not been found in bone. A high intake of calcium during the postmenopausal period (up to 1500 mg/d) also is inhibitory (Heaney, 1981), presumably because it raises the level of ionized calcium in the serum sufficiently to suppress parathormone synthesis. 

In addition to its effects on bone and kidney cells, PTH affects the transport of calcium in the cells of the intestine and the lactating mammary gland. The hormone increases the absorption of calcium from the gut and its secretion in milk. Thus parathormone resembles vitamin D in regulating calcium transport in various kinds of cell. It too may act by regulating the biosynthesis of a specific protein, since actinomycin D prevents the action of PTH on osteoclasts which results in mobilization of bone mineral. Actinomycin D, however, does not affect the increased phosphate excretion by the kidney caused by PTH, so presumably a different mechanism is involved. 

Vitamin D is essential for the action of parathormone on osteoclasts whereby bone resorption and a hypercalcaemic response are induced. For this reason parathormone is comparatively inactive in patients with rickets. The mechanism of this synergistic effect is not clear but, since actinomycin D blocks the hypercalcaemic activity of vitamin D, it may be that the vitamin induces the formation of a calcium-binding protein in osteoclasts in a similar manner to its behaviour in the intestine. Certainly excess of vitamin D has effects on bone cells similar to those of PTH in that it mobilizes bone calcium and produces hypercalcaemia. In vitamin D deficiency, production of PTH is greatly increased in an attempt to compensate for the chronic hypocalcaemia. 

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