1α,25 dihydroxycholecalciferol receptors in intestine. I. Association of 1α,25 dihydroxycholecalciferol with intestinal mucosa chromatin

P. F. Brumbaugh, M. R. Haussler

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

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 dehydroxycholecalciferol 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 hr 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 > 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.

Original languageEnglish (US)
Pages (from-to)1251-1257
Number of pages7
JournalJournal of Biological Chemistry
Volume249
Issue number4
StatePublished - 1974
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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