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Endocrinology Vol. 140, No. 1 280-285
Copyright © 1999 by The Endocrine Society

ARTICLES

Estrogen Increases 1,25-Dihydroxyvitamin D Receptors Expression and Bioresponse in the Rat Duodenal Mucosa1

Yair Liel, Shraga Shany, Patricia Smirnoff and Betty Schwartz

Department of Medicine and the Endocrine Unit (Y.L.), Clinical Biochemistry Unit (S.S.), Soroka University Hospital of Kupat-Holim and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; and Institute of Biochemistry (P.S., B.S.), Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 96100, Israel

Address all correspondence and requests for reprints to: Betty Schwartz, Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, The Hebrew University, Rehovot 96100, Israel. E-mail: bschwart{at}agri.huji.ac.il

Menopause and estrogen deficiency are associated with apparent intestinal resistance to vitamin D, which can be reversed by estrogen replacement. The in vivo influence of estrogens on duodenal vitamin D receptor (VDR) was studied in three groups of rats: ovariectomized (OVX), sham-operated, and ovariectomized rats treated daily with estrogen (40 µg/kg BW) for 2 weeks (OVX + E). Estrogen administration to OVX rats resulted in a 2-fold increase in VDR messenger RNA transcripts. 1,25(OH)2D3 was shown to bind specifically to one class of receptors in duodenal mucosal extracts, with a dissociation constant of 0.03 nM. Binding was significantly increased in duodenal extracts from OVX + E rats, compared with OVX rats (735 ± 81 vs. 295 ± 26 fmol/mg protein; P < 0.001); a comparable, 1.5- to 2-fold increase in VDR protein expression was observed in Western blot analyzes of the duodenal mucosa. Markers of VDR activity were increased in estrogen-exposed rats: calbindin-9k messenger RNA transcript content was 1.4- to 1.6-fold higher, and alkaline phosphatase activity was 1.4- to 3-fold higher in sham-operated and OVX + E, respectively, compared with OVX. 25(OH)D, 1,25(OH)2D, or PTH levels were not altered by estrogen treatment. Cumulatively, these findings suggest that estrogen up-regulates VDR expression in the duodenal mucosa and concurrently increases the responsiveness to endogenous 1,25(OH)2D. Modulation of intestinal VDR activity by estrogen, and subsequent influence on intestinal calcium absorption, could be one of the major protective mechanisms of estrogen against osteoporosis.




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