AbstractBACKGROUNDOxytocin (OT) is implicated in regulating prostate growth. OT concentrations are increased in benign, and decreased in malignant prostate disease. This study investigated whether the altered concentrations of OT present in prostate disease affect the proliferation of malignant and non‐malignant human prostate cells.METHODSThe effects of varying concentrations of OT and gonadal steroids on cell proliferation of non‐malignant prostatic epithelial (PrEC) and stromal (PrSC) cells and androgen dependent (LNCaP) and independent (PC‐3) malignant cell lines were assessed.RESULTSOT (>0.5 nmol · L−1) had no effect on PrEC proliferation when cells were cultured alone. When co‐cultured with PrSC and gonadal steroids, OT inhibited epithelial cell proliferation. OT inhibited PrSC proliferation, when cells were cultured alone. When PrSC were co‐cultured in the presence of estrogen physiological concentrations of OT were inhibitory. No effect on cell proliferation was observed with higher concentrations of OT. OT did not affect the proliferation of malignant cell lines in the absence of androgens but, in the presence of testosterone, low concentrations of OT (<1 nmol · L−1) stimulated proliferation of PC‐3 cells. Disruption of caveolae in the plasma membrane removed the inhibitory effect of OT on PrSC proliferation but did not affect the stimulatory effect of OT on PC‐3 cells cultured in the presence of androgens.CONCLUSIONSChanges in prostatic concentrations of OT that occur with aging and malignant disease may act to facilitate cell proliferation. The localization of the OT receptor within the plasma membrane modulates OT's proliferative response in the prostate. Prostate 67: 1132–1142, 2007. © 2007 Wiley‐Liss, Inc.