The mechanism of end-organ resistance to 1α,25-dihydroxycholecalciferol in the common marmoset

Publisher Website
Google Scholar
Abstract
The common marmoset, a New World monkey, requires a large amount of cholecalciferol (110 IU/day per 100 g body wt) to maintain its normal growth. In a previous report, it was demonstrated that the circulating levels of 1.alpha.,25-dihydroxycholecalciferol [1.alpha.,25(OH)2D3] in the marmosets are much higher than those in rhesus monkeys and humans, but the marmosets are not hypercalcemic. To compare the effect of the daily intake of cholecalciferol, 2 rhesus monkeys were given a large amount of cholecalciferol (900 IU/day per 100 g body wt). Their serum levels of C, 25-hydroxycholecalciferol and 24R,25-dihydroxycholecalciferol were markedly elevated, but the serum 1.alpha.,25(OH)2D3 levels remained within a range similar to those in the rhesus monkeys fed the normal diet (intake of cholecalciferol 5 IU/day per 100 g body wt). Intestinal cytosols prepared from both monkeys contained similar 3.5S macromolecules to which 1.alpha.,25(OH)2D3 was bound specifically. However, the cytosols from the marmosets contained only 1/6 as many 1.alpha.,25(OH)2D3 receptors as those from the rhesus monkeys. Furthermore, the activity of the 1.alpha.,25(OH)2D3-receptor complex in binding to DNA-cellulose was very low in the marmosets. The marmoset evidently possesses an end-organ resistance to 1.alpha., 25(OH)2D3 and is a useful animal model for studying the mechanism of vitamin D-dependent rickets, type II.