Numerous investigations have shown that FSH can induce aromatase in granulosa cells obtained from natural ovarian cycles. In contrast granulosa luteal (GL) cells obtained from patients undergoing procedures for IVF are generally insensitive to FSH-induction of aromatase. A few studies, however, have reported that GL cells can be sensitized to this gonadotrophin. In these experiments we compared the conversion of various steroid substrates - namely pregnenolone and androstenedione (4-dione), testosterone (T) or oestrone (E1)to progesterone and oestradiol (E2)respectively in cultured GL cells.
GL cells, obtained after written consent from the patients, were cultured for 48h with FCS, for a further 24h in serum-free medium with or without 5ng/ml rhCG or hFSH and for a final 4h period with fresh medium and steroid substrates.
There was a significant time- and dose-dependent conversion of all four steroid substrates. Priming with rhCG had no effect on the conversion of pregnenolone to progesterone nor did hFSH on the conversion of T to E2. In contrast hFSH markedly and significantly (P<0.001) increased the conversion of both 4-dione and E1 to E2. The addition of 4-hydroxy androstenedione, an established aromatase inhibitor, reduced the conversion of T and 4-dione to E2 by 62% and 88% respectively. The conversion of E1to E2 was significantly increased in the presence of this inhibitor. Genistein inhibited the conversion of all E2substrates. Results show that 17beta-hydroxysteroid dehydrogenase can be induced by hFSH and that the preferred pathway of oestradiol synthesis in GL cells is 4-dione via oestrone. This would agree with the evidence that aromatase has a greater affinity for 4-dione than T.
03 - 04 Dec 2001
Society for Endocrinology