Regulation of the Renal la- and 24-Hydroxylases

Vitamin D administration to vitamin D-deficient rats and chicks suppresses the I -hydroxylase and stimulates the 24-hydroxylase. This control is exerted by 1, 25-(0H)2D3 itself and the administration of 1,25-(OH)2D3 to vitamin D-defi-cient rats brings about a suppression of the ITiydroxylase and a concommitant stimulation of the 24-hydroxylase In fact, current work suggests that the 

25- (0H)2D3 induces the formation or appearance of the 244iydroxylase system These changes apparently involve RNA and protein synthesis and 1, 25-(0H)2D3 does stimulate RNA synthesis in kidney tissue Nevertheless, the mechanism and nature whereby the renal hydroxylases are regulated by 

Besides calcium and 1, 25-(0H)2D3, phosphorus plays an important role in the regulation of 1, 25-(0H)2D3 levels in blood. Maintaining rats on a low phosphorus diet results in a marked accumulation of 1,25-(OH)2D3 in blood even in the absence of the parathyroid gland Furthermore, phosphate deprivation in thyroparathy-roidectomized rats will bring about a stimulation of 1,25-(OH)2D3 accumulation in blood and tissue. Thus in thyroparathyroidectomized rats a clear inverse relationship between serum inorganic phosphorus levels and 1,2S-(OH)2D3 accumulation has been demonstrated Under conditions of low blood phosphorus, 1,25-(OH)2D3 

Recently a report has appeared which suggested that the renal 25-OH-D3-la-hydroxylase is not stimulated by phosphate deprivation However, an examination of those results revealed that the diet used was not low in phosphorus nor was the length of time to which the animals were exposed to the low phosphorus diet sufficient to stimulate the 1 -hydroxylase. Low phosphorus diets do stimulate chick renal 25-OH-D3-la-hydroxylase activity about 5-fold although the stimulation is not comparable to that produced by low calcium diets In addition, it seems quite likely that phosphate deprivation also stimulates the intestine directly inasmuch as rats maintained on 1,25-(OH)2D3 as their sole source of vitamin D still show a marked elevation of intestinal calcium transport under conditions of phosphate deprivation A similar conclusion was reached using an analog of 1,25-(0H)2D3, namely dihydrotachysterol3  

It is clear that the biochemical mechanisms whereby the vitamin D hydroxylases of the kidney are regulated have not been solved. It is nevertheless also clear that the need for calcium or the need for phosphorus will stimulate the production of 1, 25-(0H)2D3, a hormone which functions both in calcium mobilization and in phosphate mobilization. Additionally, calcium regulation is mediated for the most part by the parathyroid hormone. Finally, l,25-(OH)2D3 itself plays an important role in this regulation by inducing the 244iydroxylase and suppressing the 1-hydroxylase. 

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