Human Type 3 3α-Hydroxysteroid Dehydrogenase (Aldo-Keto Reductase 1C2) and Androgen Metabolism in Prostate Cells

• DOI: 10.1210/en.2002-0032
• Publication Date: 2003-04-22T00:14:45Z
• Authors: Tea Lanišnik Riz...; Hsueh K. Lin; Donna M. Peehl; Stephan Steckelbr...; David R. Bauman; Trevor M. Penning
• Keywords: Dihydrotestosterone; Aldo-keto reductase; Hydroxysteroid Dehydrogenases; Hydroxysteroid Dehydrogenases

Human aldo-keto reductases (AKRs) of the AKR1C subfamily function in vitro as 3-keto-, 17-keto-, and 20-ketosteroid or 3alpha-, 17beta-, 20alpha-hydroxysteroid oxidases. These AKRs can convert potent sex hormones (androgens, estrogens, progestins) into their cognate inactive metabolites vice versa. By controlling local ligand concentration may regulate steroid hormone action at prereceptor level. AKR1C2 is expressed prostate, it will catalyze nicotinamide adenine dinucleotide (NAD(+))-dependent oxidation 3alpha-androstanediol (3alpha-diol) to 5alpha-dihydrotestosterone (5alpha-DHT). This reaction potently inhibited by reduced NAD phosphate (NADPH), indicating that NAD(+): NADPH ratio cells determine whether makes 5alpha-DHT. In transient COS-1-AKR1C2 stable PC-3-AKR1C2 transfectants, 5alpha-DHT was AKR1C2. However, transfected oxidase activity insufficient surmount endogenous 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity, which eliminated 3alpha-diol androsterone. PC-3 retinol dehydrogenase/3alpha-HSD 11-cis-retinol dehydrogenase, but these enzymes did not oxidize LNCaP-AKR1C2 alter androgen metabolism due a high rate glucuronidation. primary cultures epithelial cells, levels transcripts were detected prostate cancer, from normal prostate. Thus, acts 3-ketosteroid reductase eliminate prevents activation receptor. does act an either product inhibition because cannot oxidative 17beta-HSD present. Neither AKR1C2, nor source cells.