EFFECTS OF VALPROATE-INDUCED ALTERATION OF THE GABAERGIC SYSTEM ON PULSATILE LUTEINIZING-HORMONE SECRETION IN OVARIECTOMIZED WOMEN

It is well established that valproate increases hypothalamic concentra tions of gamma-aminobutyric acid (GABA). Although little research has been done on the role of GABA in the control of pulsatile Luteinizing hormone (LH) secretion in humans, our group recently found that admini stration of valproate had no significant effect on pulsatile LH secret ion in late follicular and mid-late luteal phase normal women, However , the results of several studies of rats suggest that GABAergic regula tion of LH secretion may depend on steroid levels. The objective of th is work was to determine whether regular administration of sodium valp roate inhibits pulsatile LH secretion in ovariectomized women, Twelve women who had undergone ovariectomy for causes other than malignant tu mors were each studied in two 8 h sessions, in each of which blood sam ples were taken every 5 min. The first session was the control: for th e second, 400 mg of sodium valproate was administered every 8 h during the seven preceding days and at 08.00 h and 14.00 h on the day of the study session. Serum valproate was determined by repolarization fluor escence spectrophotometry, and LH, estradiol and progesterone by radio immunoassay. The serum LH series were subjected to a deconvolution pro cedure to reconstruct the pattern of pituitary LH secretion. Luteinizi ng hormone pulses were identified by the authors' non-parametric metho d, Control and post-valproate results were compared with regard to num ber of pulses, pulse duration, the quantity of LH secreted in each pul se, interpulse interval and mean serum LH level, There was no statisti cally significant difference between control and post-valproate result s for any of the variables considered. It is concluded that sustained serum valproate levels do not alter pulsatile secretion of LH in ovari ectomized women, This implies that, in humans, GABA is probably not a decisive factor in the regulation of the GnRH pulse generator.