title: Estrogen-induced alterations in the regulation of mineralocorticoid and glucocorticoid receptor messenger RNA expression in the female rat anterior pituitary gland and brain.
abstract: 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.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, Maywood, Illinois 60153.
authors.forename: L H
authors.initials: LH
authors.lastname: Burgess
authors.forename: R J
authors.initials: RJ
authors.lastname: Handa