Evidence for involvement of 17bèta-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D3 level in the rat

E. M. Colin, G. J.C.M. Van Den Bemd, M. Van Aken, S. Christakos, H. R. De Jonge, H. F. Deluca, J. M. Prahl, J. C. Birkenhäger, C. J. Buurman, H. A.P. Pols, J. P.T.M. Van Leeuwen*

*Corresponding author for this work

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Abstract

The sex steroid 17β-estradiol (17β-E2) has a broad range of actions, including effects on calcium and bone metabolism. This study with 3-month- old Brown Norway rats was designed to investigate the role of 17β-E2 in the regulation of calcium homeostasis. Rats were divided in four groups, sham- operated, ovariectomized (OVX), and OVX supplemented with either a 0.025-mg or 0.05-mg 17β-E2 pellet implanted subcutaneously. After 4 weeks, in none of the groups was serum calcium, phosphate, or parathyroid hormone altered compared with the sham group, while only in the OVX rats was a significant reduction in urinary calcium found. Bone mineral density and osteocalcin were modified, as can be expected after OVX and 17β-E2 supplementation. OVX resulted in a nonsignificant increase in serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Supplementation with either one of the 17β-E2 dosages resulted in an 80% reduction of 1,25(OH)2D3 and only a 20% reduction in 25- hydroxyvitamin D3 levels. OVX, as well as supplementation with 17β-E2, did not affect serum levels of vitamin D binding protein. As a consequence, the estimated free 1,25(OH)2D3 levels were also significantly decreased in the 17β-E2-supplemented group compared with the sham and OVX groups. Next, the consequences for intestinal calcium absorption were analyzed by the in situ intestinal loop technique. Although the 1,25(OH)2D3 serum level was increased, OVX resulted in a significant decrease in intestinal calcium absorption in the duodenum. Despite the strongly reduced 1,25(OH)2D3 levels (18.1 ± 2.1 and 16.4 ± 2.2 pmol/l compared with 143.5 ± 29 pmol/l for the OVX group), the OVX-induced decrease in calcium absorption could partially be restored by supplementation with either 0.025 mg or 0.05 mg of 17β-E2. None of the treatments resulted in a significant change in calcium handling in the jejunum, although the trends were similar as those observed in the duodenum. 17β-E2 did not change the VDR levels in both the intestine and the kidney. In conclusion, the present study demonstrates that 17β-E2 is positively involved in intestinal calcium absorption, and the data strengthen the assertion that 17β-E2 exerts this effect independent of 1,25(OH)2D3. In general, 17β-E2 not only affects bone turnover but also calcium homeostasis via an effect on intestinal calcium absorption.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalJournal of Bone and Mineral Research
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 1999

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