[Effect of opioids and gamma-aminobutyric acid on ovulation]

Neurons secreting gonadotropin-releasing hormone (GnRH) contain receptors of gamma-aminobutyric acid (GABA), glutamate, fibroblast-growth factor, prolactin, beta-adrenergic receptor and dopamine receptor. Oestrogens and opioid peptides have a very important influence on gonadotropin secretion, but have no their own receptors in GnRH neurons. The role and interaction between gamma-aminobutyric acid and opioids in the inhibition of ovulation were studied, using valproate (GABA agonist) and naloxone (opioid antagonist)

Groups: postmenopausal women (50), postmenopausal women on oestrogen replacement therapy, consisting of 200 mcg/day transdermally oestrogen for one month (50), and women in luteal phase of their regular menstrual cycle (50). Thirty women from each group were studied after placebo (1st day) administration, and after 300, 600 or 1200 mg of valproate (2nd day). Gonadotropins and prolactin were measured in the same way, at intervals of 24 h, on the placebo day, and on the 2nd day. The interaction between naloxone and valproate was tested in 20 women from each group; day 1-placebo; day 2-naloxon (infusion-1.6 mg/h for 6 h); day 3-naloxon infusion, preceded by 1200 mg of valproate.

Valproate. The concentration of luteinizing hormone (LH) was significantly decreased after the administration of valproate in postmenopausal women (up to 20%) and to women in luteal phase of the cycle (up to 80%). In substituted postmenopausal women there was no change in LH concentration after valproate administration. Naloxon. Naloxon infusion had no effect on LH concentration in postmenopausal women, and was significantly increased in mean serum LH in substituted postmenopausal women (52%) and in women in luteal phase of the cycle (27%). Valproate and naloxon. In women with a high oestrogen concentrations (substituted postmenopausal women) opioid blockade with naloxon (situation analogous to preovulatory phase of the cycle) contributed to the appearance of inhibitory influence of valproate on LH secretion (29.2 IU/L-after naloxone infusion; 13.2 IU/L-after administration of valproate and naloxone). In this group of patients there was no effect of valproate on LH previous secretion.

GABA may have a significant role in the inhibition of ovulation because of its inhibitory role in LH secretion in the situations when oestrogen secretion is high, and opioid concentration is low.