Valproate-induced alterations in testosterone, estradiol and progesterone secretion from porcine follicular cells isolated from small- and medium-sized ovarian follicles

The aim of the present study was to investigate whether long-term exposure to valproate (VPA) alters follicular steroidogenesis and whether or not thi s effect is dependent on the degree of follicular development. Small- and m edium-sized follicles were obtained from pig ovaries collected, respectivel y, at days 8-10 and 14-16 of oestrus cycle. Theca interna and granulosa cel ls were isolated from follicles and placed in the same well in the ratio 1 :3 with or without the VPA in doses of 100, 300 and 500 mug ml(-1). The cul ture medium was changed after 2, 4, 6 and 8 days. In both types of follicle s, VPA caused a significant and dose-dependent reduction in both testostero ne and estradiol secretion from follicular cells. In small-sized follicles, the testosterone to oestrogen ratio increased at all doses used and after all lengths of time in culture. In medium-sized follicles, a significant in crease in the testosterone to oestrogen ratio was only observed at the high est dose level. All doses of VPA caused a marked inhibition of progesterone secretion after 48 hours while during long-term VPA exposure progesterone gradually increased demonstrating luteinization of cells. In conclusion, th e present study demonstrates a direct effect of VPA on steroidogenesis. The effect seems to differ to some extent depending on the follicular stage of development. The elevated ratio of testosterone to estradiol suggests that VPA inhibits the conversion of testosterone to estradiol. (C) 2000 BEA Tra ding Ltd.