Serum calcium and vitamin D regulate 1,25-dihydroxyvitamin D3 receptor concentration in rat kidney in vivo.

Abstract

The effects of vitamin D status, serum calcium, and serum phosphorus levels on 1,25-dihydroxyvitamin D receptor levels in kidney were investigated. Weanling rats were fed for 4 weeks on a diet with various levels ofcalcium and phosphorus with or without vitamin D. The 1,25-dihydroxyvitamin )3 receptor concentration in kidney was determined by an immunoradiometric assay. In the absence ofvitamin D, total receptor concentration is increased 2-fold by an increase in serum calcium concentration. At normal serum calcium levels, the ministration of vitamin D resulted in a 5-fold increase in receptor concentration. In hypocalcemic anima, however, vitamin D did not change receptor levels. Serum phosphorus levels could not be linked to any changes in 1,25-dihydroxyvitamnin D3 receptor concentration. This study demonstrates that serum calcium levels and vitamin D regulate 1,25-dihydroxyvitamin D3 receptor concentration in vivo in kidney. On the other hand, vitamin D is unable to exert control of receptor levels in kidney under hypocalcemic conditions. 1,25-Dihydroxyvitamin D3 [1,2D3] is the main regulator ofplasma calcium and phosphorus levels (1). Vitamin D3 undergoes a two-step hydroxylation, first in the liver and then in the kidney, to form the active metabolite 1,25-(OH)2D3. The hormone acts through an intracellular receptor protein to modulate specific gene transcription in target tissues (2).One key to a better understanding of the physiological responses to vitamin D is to study regulation of the 1,25-(OH)2D3 receptor (VDR). The importance of receptor regulation is emphasized by the observations that biological response to 1,25-(OH)2D3 is a direct function of receptor number (3) and occupancy (4,5). Previous work in cell culture systems has shown that 1,25-(OH)2D3 up-regulates its own receptor (6). Regulation of the receptor has also been studied in vivo in the rat (7,8). Measured by ligand binding, 1,25-(OH)2D3 was found to have no effect on intestinal receptor levels after 24 hr and caused only a marginal increase after 5 days of treatment. The VDR in kidney, however, was significantly up-regulated at both time points.By using an immunoradiometric assay (IRMA) for total vitamin D3 receptor protein (9), we have shown a 2-fold increase in receptor protein levels in rat intestine in vivo 12 hr after intravenous administration of 1,25-(OH)2D3, although no change was detected by ligand binding (8).In this study we examined the effects of dietary vitamin D, serum calcium, and serum phosphorus on VDR concentration in rat kidney in vivo using an IRMA. We Buffers. The following buffers were used: phosphatebuffered saline (PBS), 1.5 mM KH2PO4/8.1 mM Na2HPO4, pH 8.0/137 mM NaCl/2.7 mM KCI; PBS/Triton, 0.5% Triton X-100/PBS; TE, 50 mM Tris HCl, pH 7.4/1.5 mM EDTA; TED, 5 mM dithiothreitol/TE; TEDK300, 300 mM KCIl/ TED; TEDK300/bovine serum albumin, 0.5% bovine serum albumin/0.02% NaN3/TEDK300; TEDNalS0, 150 mM NaCl/5 mM dithiothreitol'TED; homogenization buffer, 5 mM diisopropyl fluorophosphate/TEDK300. Sample Col...

Regulation of Parathyroid Vitamin D Receptor Expression by Extracellular Calcium

“…These results are not in the same line as the reported by Brown et al (9) and Sandgren and DeLuca (19), which showed that in vivo an increase in extracellular calcium was associated with upregulation of kidney VDRmRNA. The difference may be due to the fact that our results are from in vitro experiments and the results of Brown et al and Sandgren and DeLuca were obtained from in vivo experiments.…”

Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption.

“…VDR upregulation accompanies the intestinal adaptive response during chronic dietary calcium restriction (30) and may also increase or decrease in response to serum calcium (32) or PTH (33), respectively. In vitro, 1,25(OH)2D3 itself (28,29) induces an homologous up-regulation of the VDR.…”

“…In addition, studies in vitro using cell cultures (28,29) and in vivo in rats (30)(31)(32) indicate that the biological actions of 1,25 (OH)2D3 are strongly correlated with VDR number and occupancy (33,34). Therefore, the present study was undertaken to test the hypothesis that increased intestinal calcium transport in IH rats may result from an increase in intestinal cell VDR content.…”

Lithocholic acid down-regulation of NF-κB activity through vitamin D receptor in colonic cancer cells

“…As a ligand-dependent receptor, VDR expression is highly regulated by the vitamin D status [16,17]. Therefore, pretreatment of 1,25(OH) 2 (Fig.…”