Stimulation of intestinal calcium-binding-protein mRNA synthesis in the nucleus of vitamin D-deficient chicks by 1,25-dihydroxycholecalciferol

Abstract

Stimulation of intestinal calcium transport by the hormone 1,25-dihydroxycholecalciferol appears to involve RNA transcriptions and the synthesis of new proteins. Although one of these proteins has been identified as calcium-binding protein, no RNA molecules specifically induced by the hormone in the nucleus have been identified. Nuclear RNA from intestine of vitamin D-deficient chicks before and at various time intervals after treatment with the hormone or cholecalciferol was tested for its ability to code for calcium-binding protein in a cell-free system. Calcium-binding-protein mRNA could only just be detected in the intestinal nuclei 2h after dosing with these steroids which is the same time that it was first observed in the polyribosomes. Thus 1,25-dihydroxycholecalciferol induces the production of new calcium-binding protein by stimulating the formation and rapid release from the nucleus ofnew mRNA molecules for this protein. Polyribosomal translation of the mRNA continued only as long as it was being synthesized, and the maximum rate of synthesis following a pulse dose of 125 ng of the hormone was the same as that observed after prolonged stimulation with cholecalciferol. The possibility that other 1,25-dihydroxycholecalciferol-dependent events may be occurring in the nucleus in the lag period between accumulation of the hormone in the intestine and the appearance of active calcium-binding-protein mRNA, and that these may ultimately control the synthesis of that mRNA, is discussed.

Regulation by vitamin D metabolites of messenger ribonucleic acid for preproparathyroid hormone in isolated bovine parathyroid cells.

“…It is possible that the methods used for cell dispersion rendered the cells less sensitive than otherwise to vitamin D metabolites, but, by all the criteria mentioned above, the cells appear to be functioning (23,24). In the intestine, it stimulates the synthesis of calciumbinding protein mRNA and in rat calvarial bone cells, it inhibits the synthesis of procollagen mRNA.…”

Evidence for multiple effects of vitamin D3 on calcium absorption: response of rachitic chicks, with or without partial vitamin D3 repletion, to 1,25-dihydroxyvitamin D3.

“…Therefore, the ratio of labeled phosphatidylcholine to phosphatidylethanolamine was the same in the 1-hr group as in the contols but was greater thereafter. Thus, an early effect of 1,25 (7,8); that a high-affinity intracellular receptor for 1,25(OH)2D3 is present in intestine and other tissues (4); that 1,25(OH)2D3 associates with the nucleus (5); that RNA synthesis is stimulated by 1,25(0H)2D3 (27); and that the synthesis of a unique protein (CaBP) is induced (6). In fact, in vitro translation of mRNA from intestinal cytosol has revealed the presence of only one 1,25(OH)AD3-induced message, and it is for CaBP (28).…”

Regulation of calcitonin gene transcription by vitamin D metabolites in vivo in the rat.

“…The action of 1,25(OH)2D3 is classically mediated by its action on the genome of target cells by either stimulating (e.g., calcium binding protein [19], osteocalcin [20], prolactin [211), or inhibiting transcription (e.g., collagen [22], PTH [1] (Fig. 5).…”