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

The sex steroid 17 beta-estradiol (17 beta-E-2) 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 17 beta-E-2 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 17 beta-E-2 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 17 beta-E-2 supplementation. OVX resulted in a nonsignificant increase in serum 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3). Supplementation with either one of the 17 beta-E-2 dosages resulted in an 80% reduction of 1,25(OH)(2)D-3 and only a 20% reduction in 25-hydroxyvitamin D-3 levels. OVX, as well as supplementation with 17 beta-E-2, did not affect serum levels of vitamin D binding protein. As a consequence, the estimated free 1,25(OH)(2)D-3 levels were also significantly decreased in the 17 beta-E-2-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),D, serum level was increased, OVX resulted in a significant decrease in intestinal calcium absorption in the duodenum, Despite the strongly reduced 1,25(OH)(2)D-3 levels (18.1 +/- 2.1 and 16.4 +/- 2.2 pmol/l compared with 143.5 +/- 29 pmoyl 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 17 beta-E-2, 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, 17 beta-E-2 did not change the VDR levels in both the intestine and the kidney. In conclusion, the present study demonstrates that 17 beta-E-2 is positively involved in intestinal calcium absorption, and the data strengthen the assertion that 17 beta-E-2 exerts this effect independent of 1,25(OH)(2)D-3, In general, 17 beta-E-2 not only affects bone turnover but also calcium homeostasis via an effect on intestinal calcium absorption.