Evidence for Involvement of 17β-Estradiol in Intestinal Calcium Absorption Independent of 1,25-Dihydroxyvitamin D3 Level in the Rat

Abstract

The sex steroid 17␤-estradiol (17␤-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␤-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␤-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␤-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␤-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␤-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␤-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) 2 D 3 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 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 17␤-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␤-E 2 did not change the VDR levels in both the intestine and the kidney. In conclusion, the present study demonstrates that 17␤-E 2 is positively involved in intestinal calcium absorption, and the data strengthen the assertion that 17␤-E 2 exerts this effect independent of 1,25(OH) 2 D 3 . In general, 17␤-E 2 not only affects bone turnover but also calcium homeostasis via an effect on intestinal calcium absorption. (J Bone Miner Res 1999;14:57-64)

Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries

“…This lack of age-dependent differences is in accordance with findings --gained with identical study design and methodology --in cattle and goat (Riner, 2006;Singer, 2006) and several other reports (Kinyamu et al, 1997;Wood et al, 1998;Lee et al, 2003;Pazianas et al, 2003;Yamagishi et al, 2006) and in contrast to data published elsewhere (Horst et al, 1990;Ebeling et al, 1992;Liang et al, 1994;Bischoff et al, 2001;Duque et al, 2002;Holick, 2003). Since an age and/or estrogen dependent impairment of calcium resorption was detectable in elder subjects in numerous studies, a resistance to vitamin D was postulated (Kinyamu et al, 1997;Wood et al, 1998) and furthermore vitamin D-dependent (Kinyamu et al, 1997;Liel et al, 1999;Schwartz et al, 2000;Leonard et al, 2001;Duque et al, 2002;Gilad et al, 2005) and independent effects of estrogens on calcium resorption were verified (Colin et al, 1999;Eisman, 2001;Van Cromphaut et al, 2003). Thus, in future studies hormone-and age-associated effects on calcium and vitamin D metabolism in sheep should be re-examined also in senescent dams with and without hormone substitution and evaluated separately.…”

“…Vitamin D receptors are also more abundant deep in crypts than in villar cells (Clemens et al, 1988). Results are, however, controversial in some instances (Berger et al, 1988;Sandgren et al, 1991;Kinyamu et al, 1997;Wood et al, 1998;Colin et al, 1999;Sheinin et al, 2000;Leonard et al, 2001;Lee et al, 2003;Pazianas et al, 2003;Chen et al, 2006). …”

Energy Restriction Reduces Fractional Calcium Absorption in Mature Obese and Lean Rats

“…Ovarian hormone deficiency has been reported to impair gut calcium absorption in rats (21,24,25) and in post-menopausal women (26), whereas treatment with E 2 has been shown to stimulate absorption in rats (14,21) and in humans (27). In the EnR rats, uterine weights were significantly lower than those of control rats, indicating a reduced estrogenic activity with EnR.…”

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

“…In addition, it has been demonstrated that estrogen deficiency after menopause is associated with increased renal Ca 2+ loss and intestinal Ca 2+ malabsorption, which can be corrected by estrogen replacement therapy (Colin et al 1999;Gennari et al 1990;Nordin et al 1991;Prince et al 1991). Therefore, the effect of estrogen on the proteins involved in active Ca 2+ (re)absorption was investigated.…”

“…As previously mentioned, the deleterious effects of estrogen deficiency after menopause, leads to a negative Ca 2+ balance associated with renal Ca 2+ loss, intestinal Ca 2+ malabsorption and postmenopausal osteoporosis, which can be corrected with estrogen replacement therapy (Colin et al 1999;Nordin et al 1991;Prince et al 1991;Young and Nordin 1969). In addition, estrogen has been implicated in the protection against Ca 2+ nephrolithiasis via an increased reabsorption of Ca 2+ .…”