ACUTE INCREASE OF GABAERGIC NEUROTRANSMISSION EXERTS A STIMULATORY EFFECT ON GNRH GENE-EXPRESSION IN THE PREOPTIC-ANTERIOR HYPOTHALAMIC AREA OF OVARIECTOMIZED, ESTROGEN-TREATED AND PROGESTERONE-TREATED ADULT FEMALE RATS

Although gamma-aminobutyric acid (GABA) is known to play an important role in the regulation of GnRH release from the hypothalamus, GABAergic action on hypothalamic GnRH gene expression is poorly understood. The present study aims to evaluate the effects of several GABAergic compounds on GnRH mRNA and serum LH levels at the times of LH surge induced by estrogen plus progesterone treatment in long-term ovariectomized adult rats. Animals received either aminooxyacetic acid (AOAA, an inhibitor of GABA catabolism, i.p.), muscimol (GABA-A type agonist, i.c.v.) or baclofen (GABA-B type agonist, i.c.v.) 2 h prior to sacrifice. GnRH mRNA in the preoptic/anterior hypothalamic area and serum LH levels were determined by Northern blot analysis and LH radioimmunoassay, respectively. Ah of three GABA mimetics blocked the LH surge induced by estrogen plus progesterone in a dose-dependent manner. However, inhibition of GABA catabolism with AOAA in a dose range of 10-100 mg/kg b.w. increased GnRH mRNA level by 30%. Activation of GABA-A receptor with muscimol at a low dose (5 nmol) but not at high doses(10 and 30 nmol) elevated GnRH mRNA levels by 60% over the control value. Activation of GABA-B receptor with baclofen augmented GnRH mRNA levels in a dose-dependent manner. These observations indicate that acute increase of GABAergic neurotransmission may differentially regulate the release and GnRH gene expression depending on its receptor subtypes.