Oxytocin increases 5alpha-reductase activity of human prostate epithelial cells, but not stromal cells.
BACKGROUND
Oxytocin is known to modulate 5-alpha-reductase expression and has, therefore, been implicated in the etiology and novel pharmacological treatments of benign prostatic hyperplasia (BPH). These suggestions have been made in the absence of any direct evidence that oxytocin regulates expression or activity of 5-alpha-reductase isoenzymes in the human prostate. This study evaluated the effects of oxytocin on the activity and expression of 5-alpha-reductase isoenzymes I and II of human prostate stromal (PrSC; primary site of BPH development) and epithelial (PrEC) cells.


METHODS
Cell cultures were incubated with oxytocin, or oxytocin plus a specific oxytocin antagonist for 24 hr, and conversion of (3)H-Testosterone to dihydrotestosterone used to estimate total 5-alpha-reductase activity and to determine activity of both type I and type II isoenzymes. Fully quantitative real-time RT-PCR determined levels of expression of both isoenzymes following treatments.


RESULTS
Oxytocin significantly increased the total 5-alpha-reductase activity of PrEC but not of PrSC. 5-alpha-Reductase I gene expression and enzyme activity were also increased (P<0.05) in PrEC by oxytocin. Oxytocin significantly increased type II activity, but not expression, in PrEC. Oxytocin did not significantly affect 5-alpha-reductase activity or expression in PrSC.


CONCLUSIONS
Both 5-alpha-reductase I and II are expressed in normal human prostate stromal and epithelial cells. Only 5-alpha-reductase isoenzymes of prostate epithelium are modulated by oxytocin.
Assinder
S J
SJ
Discipline of Physiology, School of Medical Sciences & Bosch Institute, University of Sydney, Sydney, Australia. stephena@physiol.usyd.edu.au
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000201:enzymology* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000502:physiology*; D011467:Prostate / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology
D007527:Isoenzymes; D010121:Oxytocin; D042944:Cholestenone 5 alpha-Reductase