title: Oxytocin differentially effects 3β-hydroxysteroid dehydrogenase and 5α-reductase activities in prostate cancer cell lines.
abstract: It is known that oxytocin stimulates steroidogenesis in several organs by modulating activity of 3β-hydroxysteroid dehydrogenases (HSD3B) and steroid 5α-reductases (SRD5A). However, this has not been established in prostate cancer where these enzymes, key to local production of androgens, are increased. Analysis of both HSD3B and SRD5A activities using a live cell in situ colourimetric assay demonstrated that in PC-3 cells HSD3B activity was significantly increased by oxytocin whilst SRD5A activity was unchanged. This was confirmed in ELISA based assays of conversion of pregnenolone to progesterone and testosterone to dihydrotestosterone in cell lysates following treatment. In contrast, oxytocin significantly inhibited HSD3B activity in LNCaPs, but significantly increased activity of SRD5A, as confirmed by ELISA assays. Analysis of both cell lines by microarray and qRT-PCR determined that these changes were not due to altered gene transcription. This study demonstrates differential effects of oxytocin on the activities of key de novo steroidogenic enzymes in prostate cancer cells.
authors.affiliation: Disciplines of Physiology, School of Medical Sciences and Bosch Institute, University of Sydney, NSW 2006, Australia. Electronic address: stephen.assinder@sydney.edu.au.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Assinder
authors.affiliation: Disciplines of Physiology, School of Medical Sciences and Bosch Institute, University of Sydney, NSW 2006, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Davies
authors.affiliation: Disciplines of Physiology, School of Medical Sciences and Bosch Institute, University of Sydney, NSW 2006, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Surija
authors.affiliation: Disciplines of Physiology, School of Medical Sciences and Bosch Institute, University of Sydney, NSW 2006, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Liu-Fu
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology*; D011375:Progesterone Reductase / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology*; D013251:Steroid Isomerases / Q000378:metabolism*
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; D010121:Oxytocin; D011375:Progesterone Reductase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D013251:Steroid Isomerases
keywords: 3-Oxo-5alpha-steroid delta 4-dehydrogenase; De novo steroidogenesis; Hydroxy-delta-5-steroid dehydrogenase; Progesterone reductase; Steroid-5-alpha-reductase