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Steroid-converting enzymes in human ovarian carcinomas.

Abstract
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.
AuthorsJustin C Chura, Hyung S Ryu, Marc Simard, Donald Poirier, Yves Tremblay, Doris C Brooker, Charles H Blomquist, Peter A Argenta
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 301 Issue 1-2 Pg. 51-8 (Mar 25 2009) ISSN: 0303-7207 [Print] Ireland
PMID18723074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • ESR1 protein, human
  • Enzyme Inhibitors
  • Estrogen Receptor alpha
  • RNA, Messenger
  • Testosterone
  • Estradiol
  • 17-Hydroxysteroid Dehydrogenases
  • 3-Hydroxysteroid Dehydrogenases
  • 3 (or 17)-beta-hydroxysteroid dehydrogenase
  • Sulfatases
  • estrone sulfatase
Topics
  • 17-Hydroxysteroid Dehydrogenases (antagonists & inhibitors, genetics, metabolism)
  • 3-Hydroxysteroid Dehydrogenases (metabolism)
  • Enzyme Inhibitors (pharmacology)
  • Estradiol (metabolism)
  • Estrogen Receptor alpha (metabolism)
  • Female
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Humans
  • Neoplasm Metastasis
  • Ovarian Neoplasms (enzymology, genetics, pathology)
  • RNA, Messenger (genetics, metabolism)
  • Substrate Specificity (drug effects)
  • Sulfatases (metabolism)
  • Testosterone (metabolism)

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