1α,25-Dihydroxycholecalciferol Receptors in Intestine

Abstract

Abstract Vitamin D3 (cholecalciferol) is known to be metabolized to 1α,25-dihydroxycholecalciferol, and this sterol is thought to be the active form of the vitamin. The present report shows that administration of increasing amounts of radioactive vitamin D3 to vitamin D-deficient chicks results in a saturable binding of 1α,25-dihydroxycholecalciferol to the intestinal chromatin that parallels saturation of the calcium absorption response. The appearance of 1α,25-dihydroxycholecalciferol in the chromatin precedes the calcium absorption response by 2 to 8 hours after a physiologic dose of 1α,25-dihydroxycholecalciferol. This sterol also specifically associates with the chromatin fraction after incubation with intestinal mucosa homogenates in vitro. The chromatin fraction contains a finite number of binding sites for 1α,25-dihydroxycholecalciferol, and closely related sterols such as 25-hydroxycholecalciferol in equal concentration do not bind to this fraction; however, displacement of the hormone from the receptor can be achieved by concentrations of cholecalciferol = dihydrotachysterol2 >> 1α-hydroxycholecalciferol g 25-hydroxycholecalciferol >> 1α,25-dihydroxycholecalciferol. Pretreatment of rachitic chicks with unlabeled vitamin D3 or 1α,25-dihydroxycholecalciferol reduced the subsequent binding of radioactive 1α,25-dihydroxycholecalciferol to the intestinal chromatin in vitro. It is concluded that localization of the apparent hormonal form of vitamin D3, 1α,25-dihydroxycholecalciferol, in the nucleus of the target tissue is probably involved in the physiologic response of calcium transport.