Involvement of endogenous gabaergic system in the modulation of gonadotropin secretion in normal cycling women

To investigate whether endogenous GABA participates in the control of gonadotropin secretion during the menstrual cycle, placebo or sodium valproate (DPA), an anticonvulsant drug which enhances endogenous GABA content by blocking GABA degradation, were administered to regularly cycling women both during early follicular and midluteal phase. In a first set of experiments, the effect of DPA administration (400 mg, orally) on basal gonadotropin secretion was evaluated in 13 subjects. During early follicular phase (n = 6), no significant changes In plasma gonadotropin levels were observed after DPA or placebo administration. Conversely, during midluteal phase (n = 7), DPA administration resulted in a significant fall (p <0.01) in plasma LH concentrations, with a maximal percent decrease of 41.8 ± 6.7% after 120 min. No changes in plasma FSH levels were observed. In a second set of experiments, the effect of DPA pretreatment (400 mg, orally) on gonadotropin release stimulated by a pulse of exogenous GnRH (10 μg, iv bolus) was studied in 11 subjects. During both follicular (n = 4) and luteal phase (n = 7), DPA did not modify gonadotropin response to GnRH injected 1h after pretreatment. Finally, 8 subjects were submitted to iv injection with 10 μg GnRH 2h after pretreatment with DPA (400 mg, orally) or placebo. During both follicular (n = 4) and luteal phase (n =4), no statistical differences in gonadotropin response to GnRH were found between DPA and placebo pretreatment. These findings demonstrated that during the estrogen-progesterone (midluteal) phase of menstrual cycle, endogenous GABA is involved in the inhibitory regulation of LH secretion at a central level.