The role of GABAA receptors in the neural systems of the medial preoptic area in the control of GnRH release in ewes during follicular phase

To examine the role of (gamma)-aminobutyric acid (GABA)A receptor mediating systems in the control of gonadotropinreleasing hormone (GnRH) release from the medial preoptic area (MPOA) of ewes during the follicular phase of the estrous cycle, the extracellular concentrations of GnRH, (beta)-endorphin, noradrenaline (NE), dopamine (DA), 4-hydroxy-3methoxy-phenyl-glycol (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC) were quantified during the local infusion of muscimol and bicuculline (agonist and antagonist of GABAA receptors, respectively) to this structure. Stimulation of GABAA receptors markedly attenuated GnRH release, increased (beta)-endorphin release and noradrenergic system activity in the MPOA. The decrease of the luteinizing hormone (LH) concentration in blood plasma and LH pulse amplitude suggests that a GABAA receptor agonist in the MPOA also suppresses GnRH release from the GnRH axon terminals in the ventromedial hypothalamus/nucleus infundibularis region (VEN/NI). Blockade of GABAA receptors had no evident effect on GnRH/LH secretion but decreased (beta)-endorphin release and increased the extracellular DOPAC concentration. The suppressive influence of muscimol in the MPOA on GnRH release might be considered a net result of its direct inhibitory effect on GnRH release, indirect inhibitory influence on GnRH release through activation of the (beta)-endorphinergic system, and facilitation of GnRH neurons by increasing noradrenaline release. The results obtained during bicuculline perfusion on these systems’ activity are not sufficiently consistent to provide a clear understanding of the lack of changes in the GnRH/LH release under blockade of GABAA receptors. We conclude that the MPOA in ewes during the follicular phase is an important regulatory site where stimulation of GABAA receptors both decreases GnRH secretion and increases (beta)-endorphin release.