Estrogen-induced alterations in the regulation of mineralocorticoid and glucocorticoid receptor messenger RNA expression in the female rat anterior pituitary gland and brain.

The influence of estrogen (E) on corticosterone (CORT) receptor function in neural tissue was investigated in female Sprague-Dawley rats. This was accomplished by using a sensitive solution-hybridization RNase protection assay to examine the effect of E on the regulation of CORT receptor mRNAs. Animals were bilaterally ovariectomized (OVX), and a Silastic capsule (0.5 cm) containing 17beta-estradiol was sc implanted. Control animals received a blank capsule. Animals were killed 1, 7, or 21 days later. Anterior pituitary glucocorticoid receptor (GR) mRNA levels were significantly lower (P < 0.01) in E-treated rats at all time points examined. Hippocampal GR mRNA levels were significantly decreased below OVX values (P < 0.01) after 1 and 21 days of E treatment. Hypothalamic-preoptic area (HPOA) GR mRNA levels were significantly lower (P < 0.01) than OVX values only after 21 days of E treatment. Mineralocorticoid receptor mRNA levels were significantly lower after E treatment (P < 0.01) at all time points and in all three tissues examined. In a second study, we administered the GR-specific agonist RU 28362 (40 mug/100 g BW for 4 days) or the nonspecific agonist dexamethasone (DEX; 40 mug/100 g BW for 4 days) to OVX - and OVX + E-treated animals. The administration of RU 28362 significantly down-regulated hippocampal GR mRNA (P < 0.05) in OVX rats only. In contrast, DEX administration significantly down-regulated hippocampal GR mRNA (P < 0.05) in both control and E-treated animals. The administration of DEX or RU 28362 significantly reduced GR mRNA levels (P < 0.05) in the HPOA of OVX control animals, but not E-treated animals. Thus, E treatment results in a loss of the glucocorticoid receptor's ability to down-regulate its mRNA. These studies, combined with our earlier findings that E treatment impairs the ability of GR to down-regulate its protein (8), provide evidence that E interferes with glucocorticoid receptor function.