Effect of glucocorticoids and 1,25-dihydroxyvitamin D3 on the developmental expression of the rat intestinal vitamin D receptor gene.
In this study the ontogenesis of rat intestinal vitamin D receptor (VDR) gene expression was examined. When Northern and slot blot analyses were used to examine the expression of intestinal VDR mRNA in 15-, 18-, 22-, and 28-day-old rats, induction of VDR mRNA was not observed until 22 days postpartum. Since little is known, particularly in the neonate, concerning the in vivo regulation of VDR gene expression, we examined the possibility that glucocorticoids and/or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] could affect the developmental expression of the intestinal VDR gene. To examine the effect of glucocorticoids, rat pups received three sequential injections (one per day) of hydrocortisone (5, 2.5, and 2.5 mg/100 g BW). Hydrocortisone administration before day 14 or on days 19-21 was not effective in inducing VDR mRNA. However, a significant 3.8-fold increase in intestinal VDR mRNA was observed in rats injected with hydrocortisone from days 15-17. The hydrocortisone effective period coincides with the glucocorticoid-sensitive period of rat intestinal development. It should be noted, however, that the up-regulation of VDR was accompanied by an increase in actin mRNA, suggesting that the effect is not specific for VDR. Similarly, when rats were bilaterally adrenalectomized on day 17 (killed on day 22), a 4-fold decrease in VDR mRNA was observed, accompanied by a decrease in actin mRNA. However, when rats were injected with 1,25-(OH)2D3 (25 ng/day.100 g BW) from days 15-17, levels of intestinal VDR mRNA were significantly increased by 1.5-fold, and this change was specific for VDR mRNA. In summary, our results indicate that hydrocortisone and 1,25-(OH)2D3 can precociously induce intestinal VDR mRNA, suggesting the involvement of glucocorticoids and 1,25-(OH)2D3 in the regulation of VDR gene expression in the developing rat intestine. However, our results also indicate that the effect of glucocorticoids (unlike the effect of 1,25-(OH)2D3) is not specific for VDR mRNA, but may reflect general effects of glucocorticoids on intestinal maturation.
Lee
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Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
Szlachetka
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Christakos
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D000315:Adrenalectomy; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006854:Hydrocortisone / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development*; D009693:Nucleic Acid Hybridization; D009928:Organ Specificity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol; D006854:Hydrocortisone