Phosphates 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. 

The changes in calvarial phosphatase activities observed in animals treated with 25-(OH)D3 are totally different from those obtained with either 1.25-(OH)2D3 or 24.25—(OH)2D3. This fact indicates that physiological doses of 25-(OH)D3 may have an effect on cellular activity, independent of the conversion of this metabolite into these dihydroxyderivatives. The various effects of these vitamin D3 metabolites cannot be correlated with changes in serum calcium and/or phosphate concentrations. Among those factors other than serum calcium and phosphate concentrations that may be involved in the mechanism of action of vitamin D3 metabolites on bone phosphatase activities, the parathyroid hormone is of importance. This hormone is known to be a potent activator of bone phosphatases223,224,228. Parathormone increases the content of alkaline, neutral and acid phosphatases in mouse calvaria in vitro. Calcitonin does not prevent the increase of those enzymes while dichloromethylene diphosphonate causes a decrease in acid phosphatase and pyrophosphatase226. ... 

The effects of thyrocalcitonin in reducing the serum levels of calcium and phosphate, and in increasing the output of phosphate in the urine, have not at present been shown to be significantly influenced by any hormone other than parathormone. Milhaud ef al. (M8) found that neither the thyrocalcitonin content of the thyroid gland nor the hypo-calcemic activity brought about by administration of thyrocalcitonin was significantly altered by hypophysectomy. The presence or absence of the thyroid gland, and therefore of thyroid hormone, does not appear to influence the sensitivity of an animal to thyrocalcitonin administration, while the interrelationship, if any, to suprarenal cortical activity does not appear to have been studied as yet. 

Low levels of plasma phosphate stimulate the conversion of the 25-hydroxyl derivative to the 1,25-hy-droxyl compound, while high levels of plasma phosphate enhance the formation of the 24,25-hydroxylated derivative. The mobilization of calcium from bone seems to require both parathormone and the 1,25-hydroxylated derivative. An effect of calcitonin on... 

If vitamin D has no effect on calcium absorption, it does affect calcium mobilization and thereby restores plasma concentrations of calcium. This finding explains why vitamin D deficiency was associated with hypocalcemia. The effect on the bone seems to require a synergetic action of vitamin D and parathormone. The 1,25-hydroxylated derivative seems to be the major active compound causing calcium release from the bone. The 25-hydroxyl derivative has, however, been shown to be active as well. Finally, vitamin D increases renal proximal tubular reabsorption of phosphate in normal and vitamin D deficient animals. Consequently phosphate excretion is decreased. Inasmuch as this effect occurs in parathyroidectomized animals, the effect of vitamin D or its metabolites must be direct. Again, the active metabolites are the 25 and 1,25-hydroxy derivatives. A calcium binding protein has been isolated from the kidney cortex, but its role in renal reabsorption is not known. 

A peritoneal lavage technique was developed which permitted study of the effect of calcium and phosphate on the parathyroid. Parathyroid activity is measured by counting the development of osteoblasts in bone. Using calcium-free and phosphate-free lavage, investigators established that the calcium levels of serum control parathyroid secretion directly, and that any effect of the phosphate is indirect on parathormone secretion. 

Although the major effect of parathormone is to mobilize calcium from bone, effects on other organs have also been described. Whereas the effect of parathormone on calcium mobilization is independent of any action of the hormone on the kidney, the phospha-turic action of parathormone is likely to result from a direct effect of the hormone on tubular excretion of phosphate. Parathyroidectomy leads to a decrease in urinary excretion of phosphate, and parathormone administration increases phosphate excretion in rats. An effect on glomerular filtration of phosphate was excluded, but it was established that parathormone acts on the tubular excretion of phosphate. 

In kidney, calcitonin increases the secretion of calcium, phosphate, and sodium. The natriuretic effect of calcitonin is associated with water loss, increased urine volume, and weight loss. The effect of calcitonin on sodium excretion is different from that of parathormone. While parathormone appears to favor a sodium for hydrogen exchange, which takes place in the distal tubules, calcitonin acts on the proximal tubule by blocking sodium and chloride reabsorption [37]. 

It might be expected that increased bone resorption through the agency of PTH would also cause an increase in plasma phosphate concentration. In fact this does not occur because the hormone has an independent effect on the kidney, causing a decrease in phosphate reabsorption by the tubules and consequently an increase in its excretion. On the other hand, parathormone increases the reabsorption of calcium by kidney tubules and so reduces excretion, thus conserving the plasma calcium (Figure 30.4). 

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. 

Biologic Effect. Parathormone regulates the ionic milieu, especially the Ca++ and phosphate content of tissues and blood. A deficiency of the hormone, e.g. after parathyroidectomy, quickly results in a decrease of the Ca++ level in blood and... 

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