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| INCREASED INTESTINAL VITAMIN-D RECEPTOR IN GENETIC HYPERCALCIURIC RATS - A CAUSE OF INTESTINAL CALCIUM HYPERABSORPTION |
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| Author(s): LI XQ, TEMBE V, HORWITZ GM, BUSHINSKY DA, FAVUS MJ |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 91 Issue: 2 Pages: 661-667 Published: FEB 1993 |
| Times Cited: 72 References: 58 |
| Abstract: In humans, familial or idiopathic hypercalciuria (IH) is a common cause of hypercalciuria and predisposes to calcium oxalate nephrolithiasis. Intestinal calcium hyperabsorption is a constant feature of IH and may be due to either a vitamin D-independent process in the intestine, a primary overproduction of 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3], or a defect in renal tubular calcium reabsorption. Selective breeding of spontaneously hypercalciuric male and female Sprague-Dawley rats resulted in offspring with hypercalciuria, increased intestinal calcium absorption, and normal serum 1,25(OH)2D3 levels. The role of the vitamin D receptor (VDR) in the regulation of intestinal calcium absorption was explored in 10th generation male genetic IH rats and normocalciuric controls. Urine calcium excretion was greater in IH rats than controls (2.9+/-0.3 vs. 0.7+/-0.2 mg/24 h, P < 0.001). IH rat intestine contained twice the abundance of VDR compared with normocalciuric controls (536+/-73 vs. 243+/-42 nmol/mg protein, P < 0.001), with no difference in the affinity of the receptor for its ligand. Comparable migration of IH and normal intestinal VDR on Western blots and of intestinal VDR mRNA by Northern analysis suggests that the VDR in IH rat intestine is not due to large deletion or addition mutations of the wild-type VDR. IH rat intestine contained greater concentrations of vitamin D-dependent calbindin 9-kD protein. The present studies strongly suggest that increased intestinal VDR number and normal levels of circulating 1,25(OH)2D3 result in increased functional VDR-1,25(OH)2D3 COMPlexes, which exert biological actions in enterocytes to increase intestinal calcium transport. Intestinal calcium hyperabsorption in the IH rat may be the first example of a genetic disorder resulting from a pathologic increase in VDR. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV CHICAGO, PRITZKER SCH MED, DEPT MED, ENDOCRINOL SECT, 5841 S MARYLAND ST, BOX 28, CHICAGO, IL 60637 USA
2. UNIV CHICAGO, PRITZKER SCH MED, DEPT MED, NEPHROL SECT, CHICAGO, IL 60637 USA
3. UNIV ROCHESTER, SCH MED & DENT, NEPHROL UNIT, ROCHESTER, NY 14642 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: KM222 |
| ISSN: 0021-9738 |
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