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. 1990 Feb;126(2):1031-5. doi: 10.1210/endo-126-2-1031.

Abstract

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 less than 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 down-regulation of vitamin D receptors in the kidney.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calcitriol / blood
  • Calcitriol / pharmacology*
  • Calcium / administration & dosage*
  • Diet
  • Down-Regulation
  • Duodenum / drug effects
  • Duodenum / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Calcitriol
  • Receptors, Steroid / drug effects
  • Receptors, Steroid / metabolism*

Substances

  • Receptors, Calcitriol
  • Receptors, Steroid
  • Calcitriol
  • Calcium