Regulation of 25-Hydroxycholecalciferol-1-Hydroxylase Activity in Kidney by Parathyroid Hormone
D. R. FRASER & E. KODICEKTop of pageTHE control by vitamin D of calcium absorption in the small intestine is now considered to be mediated by the metabolite, 1,25-dihydroxycholecalciferol (1,25-DHCC). On a molar basis it has at least 3 times the activity of cholecalciferol in increasing calcium absorption in vitamin D-deficient chickens and rats1^4. There are a number of similarities between 1,25-DHCC and classical steroid hormones, for example: the chemical structure5,6, the very small quantities required for full activity (< 3 ng g_1 mucosa7) and the specific location in the target cell nucleus8. There is also an apparent involvement of RNA and protein synthesis in the intestinal action of vitamin D9-11 while 1,25-DHCC is reported to be 10 times more potent than cholecalciferol in inducing the synthesis of a calcium binding protein in chicken intestine in organ culture12. These observations have led to the working hypothesis that 1,25-DHCC acts as a steroid hormone in regulating at the level of gene transcription the synthesis of the calcium transport mechanism itself.This hormonal role for 1,25-DHCC is further supported by the finding that it is synthesized, by 1-hydroxylation of 25-hydroxycholecalciferol (25-HCC), only in the kidney13. Thus the secretion of 1,25-DHCC into the circulation and its uptake by target tissues appears to be an endocrinological control by the kidney of calcium homeostasis.