PROPERTIES AND REGULATION OF 17-BETA-HYDROXYSTEROID OXIDOREDUCTASE OFOVCAR-3, CAOV-3, AND A431 CELLS - EFFECTS OF EPIDERMAL GROWTH-FACTOR,ESTRADIOL, AND PROGESTERONE

Although there is a growing body of evidence that 17 beta-hydroxystero id oxidoreductase plays a role in the regulation of steroid levels in epithelial tumors of the endometrium and breast, our knowledge of its role in other gynecologic tumors is limited. In this investigation, th e 17 beta-hydroxysteroid oxidoreductase activity of cell lines derived from two ovarian tumors (OVCAR-3, CAOV-3) and an epidermoid tumor of the vulva (A431) was assayed under conditions which differentiate betw een 17 beta-hydroxysteroid oxidoreductase type 1, a cytosolic isoform highly specific for estradiol, and type 2, a membrane bound isoform re active with both estradiol and testosterone. On the basis of estradiol /testosterone activity ratios, all three cell lines appear to have typ e 2-like activity, with the specific activity of A431 markedly greater than that of the other cell lines. Estradiol, progesterone, or EGF, a lone or in combination, were without effect on the enzymatic activity of OVCAR-3 cells. EGF decreased the activity of CAOV-3 cells slightly. In contrast, EGF stimulated A431 17 beta-hydroxysteroid oxidoreductas e activity 7-8-fold over a 5-day exposure. Estradiol or progesterone, singly or in combination, also did not effect the enzymatic activity o f A431 cells. However, progesterone inhibited the increase in activity seen in the presence of EGF. With EGF, estradiol, and progesterone to gether, the increase in enzymatic activity was comparable to that with EGF alone. The effects of estradiol and progesterone appear to result from steroid actions following binding of EGF to low-affinity recepto rs on A431 cells. (C) 1995 Wiley-Liss, Inc.