Evidence that the self-induced metabolism of 1,25-dihydroxyvitamin D-3 limits the homologous up-regulation of its receptor in rat osteosarcoma cells

Pols, Huibert A. P.; Birkenhäger, J. C.; Schilte, J.P.; Visser, Theo J.

doi:10.1016/0167-4889(88)90170-x

Cited by 48 publications

(19 citation statements)

References 24 publications

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“…The finding of increased intestinal calcium absorption without an elevation in 1,25(OH) 2 D 3 levels led Li et al to hypothesize that alteration of the receptor for vitamin D might be responsible for the abnormal regulation of calcium by enterocytes (22,143). The intensity of 1,25(OH) 2 D 3 action correlates with receptor number and saturation (144,145) both in rats in vivo (146 -148) and in cell culture studies in vitro (149,150 Yao et al (30) found that the vitamin D receptor in the GHS rats hyperresponded to minimal doses of 1,25(OH) 2 D 3 . The hyperresponsiveness occurred through an increase in vitamin D receptor stability without involving alterations in VDR gene transcription, de novo protein synthesis, or mRNA sequence.…”

Section: Genetic Hypercalciuric Stone-forming Ratsmentioning

confidence: 99%

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

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Section: Genetic Hypercalciuric Stone-forming Ratsmentioning

confidence: 99%

Molecular Mechanisms of Primary Hypercalciuria

Frick¹,

Bushinsky²

2003

Journal of the American Society of Nephrology

127

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“…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).…”

mentioning

confidence: 99%

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

Sandgren

DeLuca

1990

Proc. Natl. Acad. Sci. U.S.A.

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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...

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“…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.…”

Section: Introductionmentioning

confidence: 99%