Evidence for involvement of 17 beta-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D-3 level in the rat

The sex steroid 17 beta-estradiol (17 beta-E-2) has a broad range of action s, including effects on calcium and bone metabolism. This study with 3-mont h-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 wee ks, in none of the groups was serum calcium, phosphate, or parathyroid horm one altered compared with the sham group, while only in the OVX rats was a significant reduction in urinary calcium found. Bone mineral density and os teocalcin were modified, as can be expected after OVX and 17 beta-E-2 suppl ementation. OVX resulted in a nonsignificant increase in serum 1,25-dihydro xyvitamin D-3 (1,25(OH)(2)D-3). Supplementation with either one of the 17 b eta-E-2 dosages resulted in an 80% reduction of 1,25(OH)(2)D-3 and only a 2 0% reduction in 25-hydroxyvitamin D-3 levels. OVX, as well as supplementati on with 17 beta-E-2, did not affect serum levels of vitamin D binding prote in. As a consequence, the estimated free 1,25(OH)(2)D-3 levels were also si gnificantly decreased in the 17 beta-E-2-supplemented group compared with t he sham and OVX groups. Next, the consequences for intestinal calcium absor ption were analyzed by the in situ intestinal loop technique. Although the 1,25(OH),D, serum level was increased, OVX resulted in a significant decrea se in intestinal calcium absorption in the duodenum, Despite the strongly r educed 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 ca lcium 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 s ignificant change in calcium handling in the jejunum, although the trends w ere similar as those observed in the duodenum, 17 beta-E-2 did not change t he VDR levels in both the intestine and the kidney. In conclusion, the pres ent study demonstrates that 17 beta-E-2 is positively involved in intestina l 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.