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Endocrinology, Vol 118, 1583-1589, Copyright © 1986 by Endocrine Society


ARTICLES

Human parathyroid hormone inhibits renal 24-hydroxylase activity of 25- hydroxyvitamin D3 by a mechanism involving adenosine 3',5'- monophosphate in rats

T Shigematsu, N Horiuchi, Y Ogura, T Miyahara and T Suda

The in vivo effect of PTH on renal 24-hydroxylase activity of 25- hydroxyvitamin D3 (25OHD3) was examined in vitamin D-deficient thyroparathyroidectomized rats by a recently developed sensitive in vitro assay of 25OHD3-hydroxylases using rat kidney homogenates and by an in vivo assay measuring the accumulation of tritiated metabolites in plasma 5 h after injection of 25OH[3H]D3. Infusion for 20 h of either human PTH-(1-34) (except at 800 pmol/h) or cAMP did not significantly change the plasma levels of calcium and phosphorus compared with those in thyroparathyroidectomized rats given 125 ng 1,25-dihydroxyvitamin D3 to induce renal 24-hydroxylase activity. On the other hand, human PTH- (1-34) markedly inhibited renal 24-hydroxylase activity and stimulated 1-hydroxylase activity. The effective concentration of human PTH-(1-34) was much lower for inhibiting 24-hydroxylase than for stimulating 1- hydroxylase activity. Infusion of less than 100 nmol/h cAMP similarly inhibited 24-hydroxylase activity without enhancing 1-hydroxylase activity. Either theophylline (1.0 mumol/h) or a submaximal dose (25 pmol/h) of human PTH-(1-34) alone inhibited 24-hydroxylase activity only slightly, but the concomitant infusion of both chemicals markedly inhibited 24-hydroxylase activity without stimulating 1-hydroxylase activity. These effects of human PTH-(1-34) and cAMP occurred similarly in both the in vitro and the in vivo assays. The present study clearly indicates that besides its well known action in stimulating 1- hydroxylase activity, PTH inhibits renal 25OHD3-24-hydroxylase activity by a mechanism involving cAMP.


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A. Matsunuma, T. Kawane, T. Maeda, S. Hamada, and N. Horiuchi
Leptin Corrects Increased Gene Expression of Renal 25-Hydroxyvitamin D3-1{alpha}-Hydroxylase and -24-Hydroxylase in Leptin-Deficient, ob/ob Mice
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Am. J. Physiol. Endocrinol. Metab.Home page
W. Yang, P. A. Friedman, R. Kumar, J. L. Omdahl, B. K. May, M.-L. Siu-Caldera, G. S. Reddy, and S. Christakos
Expression of 25(OH)D3 24-hydroxylase in distal nephron: coordinate regulation by 1,25(OH)2D3 and cAMP or PTH
Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E793 - E805.
[Abstract] [Full Text] [PDF]




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