ACTIVATION OF CENTRAL GABA(A) - BUT NOT OF GABA(B) - RECEPTORS RAPIDLY REDUCES PITUITARY LH-RELEASE AND GNRH GENE-EXPRESSION IN THE PREOPTIC-ANTERIOR HYPOTHALAMIC AREA OF OVARIECTOMIZED RATS

gamma-Aminobutytric acid (GABA) exerts an inhibitory action on gonadotropin-releasing hormone (GnRH) release from the hypothalamus. In vivo, this inhibitory action appears to be mediated via the GABA(A) receptor since in ovariectomized (ovx) rats and sheep direct application of muscimol (MUS), a GABA(A) agonist, into the preoptic area (POA), th site were the GnRH cell bodies are located, caused an immediate reduction of LH release. This effect may be the result of an inhibition of GnRH release but also GnRH biosynthesis may be affected. Using competitive reverse transcription-polymerase chain reaction (RT-PCR) we now addressed the question, whether an acute inhibition of the GnRH pulse generator in ovx rats by GABA involves reduction of GnRH biosynthesis as determined by GnRH mRNA levels in micropunches of the POA. To activate either the GABA(A) or GABA(B) receptor, we injected intraventricularly (icv) MUS or baclofen (BAC). Intracerebroventricular injection of 10 nmol MUS caused a rapid and lasting inhibition of LH release from about 7.5 ng/ml (pretreatment value) to approximately 1.5 ng/ml. Neither application of BAC or saline (control injections) affected LH secretion. Two hours after icv injections, rats were decapitated and GnRH mRNA levels were determined. MUS induced a pronounced decrease of GnRH levels in the POA (control rats: 2.26 pg GnRH mRNA; MUS-treated rats: 0.85 pg, n = 10/ group). BAC was without any effect on GnRH mRNA levels. Thus, we confirm the inhibitory action of GABA on LH release in vivo which is exerted via the A-subtype of the receptor. We suggest that this effect, in addition to the possible actions of MUS on other neuronal systems relevant to central regulation of LH secretion, is at least in part due to a similarly rapid suppression of GnRH gene expression in the POA and/or accelerated GnRH mRNA turnover.