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JESSE P. GOFF, TIMOTHY A. REINHARDT, MATTHEW J. BECKMAN, RONALD L. HORST, Contrasting Effects of Exogenous 1,25-Dihydroxyvitamin D [1,25-(OH)2D] Versus Endogenous 1,25-(OH)2D, Induced by Dietary Calcium Restriction, on Vitamin D Receptors, Endocrinology, Volume 126, Issue 2, 1 February 1990, Pages 1031–1035, https://doi.org/10.1210/endo-126-2-1031
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The biological actions of 1,25-dihydroxyvitamin D [1,25-(OH)2D] are mediated by specific binding of the hormone with an intracellular vitamin D receptor, which ultimately regulates expression of genes within the target tissues. The quantity of vitamin D receptors varies between target tissues and within target tissues, depending on the physiological state of the animal. One factor that can modulate tissue vitamin D receptor content is 1,25-(OH)2D. In the present study performed in male rats, exogenous administration of 36 ng 1,25-(OH)2D3/ day for 7 days increased plasma 1,25-(OH)2D concentrations 5- fold above those in control rats (to 261 ± 17 pg/ml). Compared with those in control rats, 1,25-(OH)2D3 treatment resulted in a 1.5-fold increase in duodenal vitamin D receptor content (351 ± 16 vs. 520 ± 21 fmol/mg protein) and a 3-fold increase in renal vitamin D receptor content (60.3 ± 5.2 vs. 193.8 ± 22.7 fmol/mg protein). The effects of endogenously produced 1,25-(OH)2D on tissue vitamin D receptor content were studied by feeding rats either a 0.02% or 1% calcium diet for 2, 7, 14, or 21 days. Rats fed the low calcium diet exhibited plasma 1,25-(OH)2D concentrations similar to (day 7) or exceeding (days 14 and 21) those achieved by exogenous administration of 1,25-(OH)2D3, yet duodenal vitamin D receptor content was not up-regulated by dietary calcium restriction at any time point. The renal vitamin D receptor content of calcium restricted rats was 20-38% lower (p < 0.05) than that in rats fed a calcium-replete diet 7, 14, and 21 days after initiation of the dietary treatments. These data suggest that under physiological conditions, increased plasma concentrations of 1,25-(OH)2D do not result in up-regulation of tissue vitamin D receptor concentrations, and that dietary calcium restriction must induce some factor(s) that results in downregulation of vitamin D receptors in the kidney. (Endocrinology126: 1031–1035, 1990)
