ESTROGEN REGULATION OF GABA(A) RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN PREOPTIC AREA AND BED NUCLEUS OF THE STRIA TERMINALIS OF FEMALERAT-BRAIN

This study has examined whether circulating estrogens are involved in regulating gamma-aminobutyric acid (GABA)(A) receptor mRNA expression in regions of the female rat brain known to contain estrogen receptors (ERs). In situ hybridization experiments using S-35-labeled oligonucl eotides specific for alpha(2), beta(3), and gamma(1) subunit mRNAs of the GABA(A) receptor demonstrated that all three mRNAs were abundant i n only the medial preoptic nucleus (MPN), where they were expressed by the vast majority of cells, and specific regions of the bed nucleus o f the stria terminalis including the principle encapsulated nucleus (P rN-BNST) and bed nucleus of the anterior commissure (BNAC). Estrogen t reatment of ovariectomized rats for 7 d resulted in significant 30-60% increases in alpha(2) and gamma(1), but not beta(3), subunit mRNA exp ression in the MPN and PrN-BNST. Estrogen treatment for 24 hr resulted in levels of mRNA expression intermediate between those of controls a nd animals treated with estrogen for 7 d. No changes in subunit mRNA e xpression were detected for any subunit in the BNAC or cingulate corte x. Double-labeling immunocytochemistry experiments using antibodies di rected against the alpha(2) subunit of the GABA(A) receptor and the ER , revealed that 67 +/- 3% of alpha(2) subunit-immunoreactive cells in the MPN also contained ER immunoreactivity, Cells expressing alpha(2) subunits in the PrN-BNST were also found to possess ERs while those in the BNAC and cingulate cortex did not. These findings suggest the pos sibility that ER-containing cells in the MPN and PrN-BNST express an a lpha(2) beta(3) gamma(1) isoform of the GABA(A) receptor that has its alpha(2) and gamma(1) subunits regulated by circulating estrogen conce ntrations. Together, our observations indicate that estrogen may regul ate GABA(A) receptor mRNA expression at a transcriptional level and th at this is only likely to occur within regions of the rat brain posses sing ERs.