The mechanism of end-organ resistance to 1 alpha,25-dihydroxycholecalciferol in the common marmoset.
The common marmoset, a New World monkey, requires a large amount of cholecalciferol (110 i.u./day per 100g body wt.) to maintain its normal growth. In a previous report, we 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 hypercalcaemic [Shinki, Shiina, Takahashi, Tanioka, Koizumi & Suda (1983) Biochem. Biophys. Res. Commun. 14, 452-457]. To compare the effect of the daily intake of cholecalciferol, two rhesus monkeys were given a large amount of cholecalciferol (900 i.u./day per 100g body wt). Their serum levels of calcium, 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 i.u./day per 100g body wt). Intestinal cytosols prepared from both monkeys contained similar 3.5 S macromolecules to which 1 alpha,25(OH)2D3 was bound specifically. However, the cytosols from the marmosets contained only one-sixth 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. These results suggest that the marmoset 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.
Takahashi
N
N
Suda
S
S
Shinki
T
T
Horiuchi
N
N
Shiina
Y
Y
Tanioka
Y
Y
Koizumi
H
H
Suda
T
T
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002144:Callithrix / Q000378:metabolism*; D002143:Callitrichinae / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D002762:Cholecalciferol / Q000097:blood; D002852:Chromatography, Ion Exchange; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D004351:Drug Resistance; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010758:Phosphorus / Q000097:blood; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002762:Cholecalciferol; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium