Steroid-converting enzymes in human ovarian carcinomas

Anti-estrogen therapies for treating ovarian carcinoma have had mixed outcomes suggesting some tumors may be estrogen-dependent. We assayed the activity levels of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17 beta-HSD activity ratios with estradiol (E-2) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17 beta-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17 beta-HSD, 3 alpha-HSD/3-KSR, and 3 beta-HSD. E-2/T activity ratios varied widely between samples. A 17 beta-HSD type 1 inhibition pattern was observed in 23% of the samples and a type 2 pattern in 25%. E-2 formation from estrone sulfate ((ES)-S-1) was detected in 98% (47/48) of the samples. 17 beta-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17 beta-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy. (c) 2008 Elsevier Ireland Ltd. All rights reserved.