Ovarian hormone deficiency decreases and estrogen (E2) and growth hormone (GH) administrations increase intestinal absorption of calcium (Ca++). However, the underlying mechanisms are uncertain. To examine whether alterations in the binding characteristics of intestinal estrogen receptors (ERs) are involved, we developed and validated methods for simultaneous measurement of intestinal ERs in cytosolic and nuclear fractions and applied these techniques to four groups of female rats: sham-operated, ovariectomized (Ovx), Ovx + 5 μg E2/kg b.wt./day and Ovx + 8 mg GH/kg. b.wt./day. All animals were killed on day 21, and mucosal cells harvested from the duodenum for ER determination. The cytosolic and nuclear ERs were 117.2 ± 2.7 fmol/mg protein and 64.9 ± 1.2 fmol/mg DNA, respectively, in sham-operated rats and decreased by 16.1% and 17.0% to 98.4 ± 1.7 fmol/mg protein and 53.8 ± 1.3 fmol/mg DNA, respectively in Ovx rats (P < .001). E2 therapy prevented completely the decrease in cytosolic and nuclear ERs that occurred in Ovx rat (126.1 ± 2.9 fmol/mg protein and 68.0 ± 3.0 fmol/mg DNA, respectively, in the E2-treated group). Similarly, GH administration prevented the decrease in cytosolic and nuclear ERs that resulted from ovariectomy (119.2 ± 3.2 fmol/mg protein and 63.4 ± 1.3 fmol/mg DNA, respectively, in the GH-treated group). The K(d) of nuclear ER-ligand complex was 2.0 ± 0.03 nM in sham-operated rats and was slightly modulated by Ovx, E2 and GH (3.3 ± 0.02, 2.33 ± 0.09 and 2.23 ± 0.04 nM, respectively, P < .001), but the K(d) of cytosolic ER-ligand complex was not altered by Ovx, E2 or GH. Our findings indicate that E2 deficiency down-regulates, whereas E2 and GH administrations up-regulate intestinal ERs and prevent ovariectomy-induced decrease in receptor binding affinity. We conclude that E2 deficiency, E2 and GH may modulate intestinal Ca++ absorption, in part, by altering the abundance and binding characteristics of intestinal ERs.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jul 1998|
ASJC Scopus subject areas
- Molecular Medicine