Article Document Academic Article Information Content Entity Continuant Continuant Journal Article Entity Entity Generically Dependent Continuant 2025-05-09T14:59:48 RDF description of Androgenic and estrogenic 17beta-hydroxysteroid dehydrogenase/17-ketosteroid reductase in human ovarian epithelial tumors: evidence for the type 1, 2 and 5 isoforms - http://repository.healthpartners.com/individual/document-rn18429 2022-02-21T22:48:57.408-06:00 23880 Diethylstilbestrol/pharmacology RNA, Messenger/metabolism public Adenocarcinoma, Mucinous/*enzymology 81 <p>17beta-Hydroxysteroid dehydrogenase/17-ketosteroid reductases (17HSD/KSR) play a key role in regulating steroid receptor occupancy in normal tissues and tumors. Although 17HSD/KSR activity has been detected in ovarian epithelial tumors, our understanding of which isoforms are present and their potential for steroid metabolism is limited. In this investigation, 17HSD/KSR activity from a series of ovarian epithelial tumors was assayed in cytosol and microsomes under conditions which differentiate between isoforms. Inhibition studies were used to further characterize the steroid specificities of isoforms in the two subcellular fractions. Activity varied widely between tumors of the same histopathologic classification. The highest levels of activity were observed in mucinous tumors. Michaelis constants, maximum velocities, estradiol-17beta/testosterone (E(2)/T) activity ratios and inhibition patterns were consistent with a predominance of microsomal 17HSD/KSR2 and cytosolic 17HSD/KSR5, isoforms reactive with both E(2) and T, with evidence of estrogenic 17HSD/KSR1 in cytosol from some samples. In tumors where activity and mRNA expression were both characterized, Northern blots, PCR and sequence analysis indicated 17HSD/KSR5 was the predominant isoform. The presence of 17HSD/KSR5, which also has both 3alpha-HSD/KSR and 20alphaHSD/KSR activity, and 17HSD/KSR2 which also has 20alpha-HSD activity, could influence not only estrogen and androgen binding but progesterone receptor occupancy, as well, in receptor-containing tumors.<p> Androgens/pharmacology Isoenzymes Epithelial Cells/enzymology Microsomes/drug effects/enzymology 17-Hydroxysteroid Dehydrogenases/genetics/*metabolism Reverse Transcriptase Polymerase Chain Reaction document-rn18429 Androgenic and estrogenic 17beta-hydroxysteroid dehydrogenase/17-ketosteroid reductase in human ovarian epithelial tumors: evidence for the type 1, 2 and 5 isoforms Blotting, Northern DNA, Complementary RNA, Neoplasm/metabolism DNA Primers/chemistry Tumor Cells, Cultured/drug effects/metabolism 4-5 10.1016/s0960-0760(02)00117-6 Journal of Steroid Biochemistry and Molecular Biology Testosterone/pharmacology Estrogens/pharmacology Cytosol/drug effects/enzymology Ovarian Neoplasms/*enzymology 14650 Antineoplastic Agents, Hormonal/pharmacology