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Modulation of intestinal estrogen receptor by ovariectomy, estrogen and growth hormone
1Department of Physiology, University of Texas Health Science Center, San Antonio, USA.
Abstract:
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 micrograms 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 Kd 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 Kd 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.
Insights
Ovarian hormone deficiency reduces intestinal estrogen receptors (ERs). Estrogen (E2) and growth hormone (GH) treatments increased ERs and improved calcium absorption, suggesting a key role for ERs in hormonal regulation.
Area of Science:
- Endocrinology
- Gastroenterology
- Molecular Biology
Background:
- Ovarian hormone deficiency is known to decrease intestinal calcium absorption.
- Estrogen (E2) and growth hormone (GH) administration are known to increase intestinal calcium absorption.
- The precise mechanisms by which E2 and GH influence calcium absorption remain unclear.
Purpose of the Study:
- To investigate the role of intestinal estrogen receptors (ERs) in mediating the effects of ovarian hormones on calcium absorption.
- To determine if alterations in the binding characteristics of intestinal ERs are involved in the observed changes in calcium absorption.
Main Methods:
- Developed and validated methods for simultaneous measurement of cytosolic and nuclear intestinal ERs.
- Applied these methods to four groups of female rats: sham-operated, ovariectomized (Ovx), Ovx + E2, and Ovx + GH.
- Determined ER levels and binding affinity (Kd) in duodenal mucosal cells after 21 days of treatment.
Main Results:
- Ovariectomy significantly decreased both cytosolic and nuclear ER levels in rat intestinal cells.
- Estrogen (E2) and growth hormone (GH) administration completely prevented the ovariectomy-induced decrease in ER abundance.
- Ovariectomy slightly modulated the binding affinity of nuclear ERs, while E2 and GH treatments normalized this affinity.
Conclusions:
- Estrogen deficiency down-regulates intestinal estrogen receptors.
- Estrogen (E2) and growth hormone (GH) administrations up-regulate intestinal ERs and normalize their binding characteristics.
- These alterations in intestinal ERs likely play a significant role in modulating intestinal calcium absorption under varying hormonal conditions.