Modulation of intestinal vitamin D receptor by ovariectomy, estrogen and growth hormone

Age-related decline in intestinal calcium (Ca) absorption often occur in postmenopausal osteoporotic women. The impaired Ca absorption can be corrected by estrogen (E2) therapy. Growth hormone (GH) therapy has also been reported to increase intestinal absorption of calcium. Since 1,25-dyhydroxyvitamin D (1,25(OH)2D) is the primary regulator of calcium absorption, we explored whether the mechanisms by which E2 and GH enhance Ca absorption involves the vitamin D endocrine system. We measured serum 1,25(OH)2D concentrations and determined the binding characteristics of intestinal vitamin D receptors (VDRs) in four groups of female rats: sham operated (sham), ovariectomized (ovx), ovx + E2, and ovx + GH. Serum 1,25(OH)2D levels were 42.4 +/- 3.4 and 42.5 +/- 3.2 pg/ml in sham and ovx rats, respectively, and decreased by 63 and 34% (P < 0.001) in ovx + E2 and ovx + GH-treated rats, respectively. The numbers of total, unoccupied and occupied VDRs were 116.9 +/- 2.0, 72.1 +/- 1.1 and 44.8 +/- 1.9 fmol/mg protein, respectively, in sham operated rats, and decreased significantly following ovariectomy by 24, 27 and 19% (P < 0.01), respectively. E2 therapy not only significantly increased total, unoccupied and occupied VDRs above those of ovx rats by 55, 58 and 49% respectively, but it increased the levels above those of sham operated controls as well (P < 0.01). In contrast, GH administration prevented the decrease that occurred in ovx rats in the number of total and unoccupied VDRs (111.2 +/- 3.3; 72.6 +/- 1.4 fmol/mg protein, respectively), but it had no significant effect on the number of occupied VDRs. The dissociation constant (Kd) of intestinal VDRs was unaltered by ovariectomy, E2 and GH. We conclude that down regulation of intestinal VDRs may contribute to the Ca malabsorption that occurs in ovarian hormone deficient states such as postmenopausal osteoporosis, and that the stimulation of Ca absorption by E2 and GH may result, in part, from up regulation of intestinal VDRs.