Neurosteroid Synthesis-Mediated Regulation of GABA A Receptors: Relevance to the Ovarian Cycle and Stress

The study demonstrated that both ovarian and stress hormones could reorganize GABA A receptors (GABA A Rs) through neurosteroid metabolites. In female mice, cyclic changes in GABA A Rs correlated with progesterone levels, and similar effects were observed in males and ovariectomized females treated with exogenous progesterone. Progesterone increased GABA A R δ subunit expression and tonic inhibition in dentate gyrus granule cells, effects blocked by finasteride, indicating neurosteroid synthesis, not progesterone receptor activation, was responsible. Neurosteroids rapidly altered GABA A R expression, as shown by in vitro brain slice experiments and acute stress conditions, which quickly elevated neurosteroid levels and GABA A R δ subunit expression.