DIFFERENTIAL EXPRESSION OF GAMMA-AMINOBUTYRIC-ACID RECEPTORS IN IMMORTALIZED LUTEINIZING-HORMONE-RELEASING HORMONE NEURONS

Gamma-Aminobutyric acid (GABA) has been shown both to stimulate and in hibit LH secretion in vivo. GABA apparently exerts these effects at th e hypothalamic level by regulating the release of LHRH. In this study, we have investigated the effect of GABAergic agents on LHRH secretion from an immortalized hypothalamic neuronal cell line (GT1-7). LHRH se cretion was stimulated in a dose-dependent manner with increasing conc entrations of GABA. This effect was mimicked by the GABA(A) receptor a gonist, muscimol, and was blocked by the selective antagonist, bicucul line. The stimulatory effect of muscimol on LHRH secretion was synergi stic with low concentrations of [K+]. By comparison, neither activatio n of the GABA(B) receptors with baclofen nor blockade with phaclofen i nfluenced basal LHRH secretion. Baclofen, however, did depress [K+]-in duced LHRH release. Binding studies confirmed the presence of GABA(A) and GABA(B) receptors on GT1-7 cells. In addition, Northern blots with probes to the GABA(A) receptor alpha1, beta3, and gamma2L subunits re vealed that only the beta3 messenger RNA (MRNA) was expressed in the G T1-7 cells. These data provide the first demonstration that immortaliz ed LHRH neurons are directly responsive to GABAergic agents. To the ex tent that these immortalized neurons may resemble those in vivo, our r esults suggest that GABAergic agents may play a dual role in reproduct ive physiology by exerting both stimulatory and inhibitory control ove r LHRH release.