Human parathyroid hormone inhibits renal 24-hydroxylase activity of 25-hydroxyvitamin D3 by a mechanism involving adenosine 3',5'-monophosphate in rats.
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.
D015650:24,25-Dihydroxyvitamin D 3; D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000201:enzymology*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019379:Teriparatide; D013806:Theophylline / Q000494:pharmacology; D013965:Thyroidectomy; D013997:Time Factors; D065668:Vitamin D3 24-Hydroxylase
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D015650:24,25-Dihydroxyvitamin D 3; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol