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 17beta-hydroxysteroid dehydrogenase (17beta-HSD), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD/3-KSR) and estrone sulfatase in a series of ovarian epithelial carcinomas. 17beta-HSD activity ratios with estradiol (E(2)) and testosterone (T), and inhibition by isoform-specific inhibitors were used to estimate the contributions of 17beta-HSD isoforms. Activity levels were highest for estrone sulfatase, followed, respectively by 17beta-HSD, 3alpha-HSD/3-KSR, and 3beta-HSD. E(2)/T activity ratios varied widely between samples. A 17beta-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 (E(1)S) was detected in 98% (47/48) of the samples. 17beta-HSD type 1, type 2 and type 5 mRNA was detected in matched primary tumor and metastases. Evaluation of 17beta-HSD and sulfatase activity levels, activity ratios and inhibition patterns may help predict tumor response to endocrine therapy.
Chura
Justin C
JC
Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN, USA.
Ryu
Hyung S
HS
Simard
Marc
M
Poirier
Donald
D
Tremblay
Yves
Y
Brooker
Doris C
DC
Blomquist
Charles H
CH
Argenta
Peter A
PA
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity / Q000187:drug effects; D013429:Sulfatases / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
C506487:ESR1 protein, human; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013429:Sulfatases; C020121:estrone sulfatase