VALPROATE INDUCES HYPERANDROGENISM IN BOTH BASAL AND GONADOTROPIN-STIMULATED PORCINE OVARIAN FOLLICULAR CELLS
Abstract number :
2.343
Submission category :
Year :
2003
Submission ID :
3808
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Erik Tauboll, Ewa L. Gregoraszczuk, Anna Kolodziej, Malgorzata Kajta, Erik Ropstad Department of Neurology, Rikshospitalet, University of Oslo, Oslo, Norway; Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland; D
Long-term valproate (VPA) treatment has been associated with hyperandrogenism and polycystic ovaries in women with epilepsy. The exact mechanisms of action of the drug on sex steroid hormone function are still unsettled. The aim of the present study was to investigate the action of VPA on basal and gonadotropin stimulated steroid secretion in porcine ovarian follicular cells, and to measure the conversion of testosterone to estradiol.
Small and medium sized follicles were obtained from pig ovaries on days 8-10 and 14-16 of the oestrus cycle. Both follicular compartments, theca and granulosa cells, were cultured as a co-culture resembling follicles in vivo. VPA in concentrations of 100 and 250 mg/ml was added to the control or gonadotropin-stimulated cultures.
VPA caused a significant increase in basal and LH-stimulated testosterone secretion from small follicles. In medium follicles an increased basal, but decreased LH-stimulated testosterone secretion was found. VPA caused decreased basal and FSH-stimulated estradiol secretion by small follicles while only the higher concentration decreased estradiol secretion in medium follicles. The conversion of testosterone to estradiol by small follicles was decreased under the influence of VPA in testosterone alone and in testosterone plus FSH stimulated cultures. This was only seen at the higher VPA concentration in medium follicles.
VPA altered steroidogenesis in both unstimulated and gonadotropin-stimulated porcine ovarian follicular cells and inhibited the conversion of testosterone to estradiol. These changes may be of importance in the development of VPA induced hyperandrogenism