Kidneys parathormone effect

Electrolyte movements in general, but calcium movements in particular, are important in mitochondrial physiology. (The movement of electrolytes in and out of mitochondria will be discussed in another chapter.) However, parathormone s effect on calcium movements in kidney and liver mitochondria is relevant to the possible mode of action of the hormone on the kidney. Parathormone has a complex effect on isolated liver and kidney mitochondria. Not only does the hormone stimulate calcium release from mitochondria, but this effect on the divalent cation is associated with all sorts of changes in the electrolyte composition of the mitochondria, and with altering mitochondrial metabolism. When incubated with the hormone, the mitochondria swell and take up potassium, ATP is hydrolyzed, and the ATP-Pj exchange is blocked. 

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. 

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. 

The major effect of parathormone is to maintain the calcium levels of serum constant by acting on at least three target organs bone, kidney, and the barrier between the plasma and extracellular fluid. It is now generally accepted that parathormone primary affects bone. 

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. 

Hormonal Regulation of Kidney Function. Three different hormones act on the kidney the adrenocortical hormone (mineralcorticoid effect, cf. Chapt. XX-2), the parathyroid hormone (parathormone, cf. Chapt. XX-7), and the antidiuretic hormone (ADH, vasopressin, cf. Chapt. XX-9) of the hypophyseal posterior lobe. 

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