Recent advances in vitamin D metabolism: 1,25-Dihydroxycholecalciferol, a kidney hormone controlling calcium metabolism

Abstract

The action of vitamin D in healing rickets is associated with an increased absorption of calcium from the intestine and with a direct effect on calcium metabolism in bone. Other likely target organs are the kidney and, possibly, striated muscle. The basic question which originally motivated the investigations of vitamin D metabolism was the occurrence of a lag period of at least 10 hours between administration of vitamin D and its physiological effects. It was agreed that the lag period might be due partly or entirely to the time required for the adequate formation of a protein carrier for calcium transport. There was, of course, the other possibility that a transformation of the vitamin into an active molecule might add to the time lag. As has been shown by now, both working hypotheses were correct: calcium-binding protein(s) have been found that are dependent on the vitamin D status (Wasserman and Corradino, 1971), and 1,25-dihydroxycholecalciferol (1,25-DHCC) has been isolated and identified as the active, hormone-like molecule which is formed from its precursor, 25-hydroxycholecalciferol (25-HCC) by a special hydroxylation reaction in the kidney. The latter can thus be considered an endocrine organ for the elaboration of 1,25-DHCC, a hormone which finds its way to the target organs. Eight years ago, Eisenstein and Passavoy (1964) reported that actinomycin D inhibited Ca2 + transport in everted intestinal sacs; this was followed and confirmed by observations from a number of laboratories (for literature, see Lawson, 1971) which showed among other things that if vitamin D was given early enough, the nuclear inhibitor had no effect. These findings focused the attention on nuclear events in the interpretation of vitamin D action. It could be shown that vitamin D, added in vivo, increased the uptake of orotic acid into nuclear and total RNA and increased the template activity of DNA (Norman, 1966; Stohs, Zull and DeLuca, 1967; Lawson et al 1969c; Hallick and DeLuca, 1969). Tables 1 and 2 show the effects of vitamin D administration on the orotic acid uptake observed by the Cambridge group.