A novel mechanism for the induction of aromatase in ovarian cells in vitro: Role of transforming growth factor alpha-induced protein tyrosine kinase

In the developing follicle, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are the primary stimulators of steroidogenesis in granulosa and theca cells. The steroidogenic actions of both these gonadotropins are largely if not exclusively mediated through cAMP. Previous studies have shown that EGF and TGFα do not affect basal estrogen production but attenuate FSH-stimulated estrogen production in vitro in rat granulosa cells. Here we present evidence that TGFa stimulates basal estrogen production in prepubertal porcine ovarian granulosa and theca cells in culture under defined conditions. In granulosa cells, TGFα is more potent than FSH in stimulating estrogen production. LH does not stimulate estrogen production in prepubertal porcine theca cells but rather attenuates that stimulated by TGFα. Treatment of follicular cells with genistein (inhibitor of protein tyrosine kinase) attenuates TGFα-induced estrogen biosynthesis suggesting that the action of TGFα is mediated through protein tyrosine kinase. These studies provide evidence for an alternative cAMP-independent and TGFα-induced tyrosine kinase-dependent mechanism for the induction of ovarian aromatase.