The function and the expression of forebrain GABA(A) receptors change with hormonal state in the adult mouse

Neurotransmission mediated by gamma-aminobutyric acid type A (GABA(A)) receptors in the mammalian medial preoptic area (mPOA) plays a pivotal role in the expression of hormone-sensitive behaviors. Hand in hand with GABAergic control of reproduction, hormone treatments that activate gonadal steroid signaling pathways in gonadectomized rats are known to regulate the expression of specific GABA(A) receptor subunit mRNAs. While the effects of exogenous hormone treatments have been well documented, little information is available as to how GABA(A) receptor-mediated transmission in the mPOA is altered by endogenous changes in hormonal state in gonadally-intact adult animals or if those changes can be ascribed to hormone-dependent changes in receptor subunit composition. In the present study, we found that both the peak amplitudes of GABA(A) receptor-mediated synaptic currents in the mPOA, as well as the ability of the endogenous neurosteroids to modulate those currents, varied as a function of the estrous cycle. Moreover, we found that the degree of neurosteroid modulation was also significantly different between wild-type and the androgen-insensitive testicular feminization (Tfm) mutant male mice. Semiquantitative RT-PCR analysis performed to assess levels of GABA(A) receptor subunit mRNAs indicated that levels of specific subunits varied over the course of the estrous cycle and between wild-type and Tfm male mice. The variations in GABA(A) receptor expression and function in the mPOA that are associated with differences in gonadal steroid signaling may contribute to the dynamic nature of GABAergic control of neuroendocrine pathways.