Implication of GABA-ergic system on GnRH and GnRHR biosynthesis and LH secretion in the hypothalamic-pituitary unit of follicular-phase ewes

INTRODUCTION: An inverse relationship between GnRH transcript level and GABA neuronal activity has been suggested; in particular, that GABA at the hypothalamic level may exert a suppressive effect on subsequent steps of GnRH biosynthesis. This inhibitory action of GABA seems to be mediated mainly via a GABA type A receptor (GABAAR) mechanism. AIM(S): In the present study, we analysed the effects of GABAAR activation or inhibition on the levels of post-translational products of the genes encoding the GnRH ligand and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit of follicular-phase ewes using an in vivo infusion model. METHOD(S): Prolonged intermittent infusions of small doses of the GABAAR agonist, muscimol, or an antagonist, bicuculline, were performed into the third cerebral ventricle of ewes. Enzyme‑linked immunosorbent assay (ELISA) was used to investigate the effects of drugs on GnRH and GnRHR levels in the preoptic area (POA), anterior (AH) and ventromedial (VMH) hypothalamus, stalk/median eminence (SME), and GnRHR in the anterior pituitary gland (AP). The radioimmunoassay (RIA) method was also chosen for determining the level of LH in blood plasma. RESULTS: The study showed that activation or blockade of GABAAR significantly decreased or increased, respectively, GnRH concentration in all analysed structures and led to analogous changes in plasma LH concentration. Similar muscimol‑ and bicuculline‑related alterations were observed in the levels of GnRHR. CONCLUSIONS: On the basis of these results, it is suggested that the GABAergic system in the hypothalamus of follicular-phase sheep affects GnRH and GnRHR biosynthesis either directly or via GABAergic-sensitive interneurons, leading to suppression in the secretory activity of the hypothalamic‑pituitary GnRH/LH system.