Modulating the paracrine effects of bone marrow mesenchymal stem cells (BMSC) may be important for the treatment of ischemic myocardial tissue. In this regard, endogenous estrogen may enhance BMSC vascular endothelial growth factor (VEGF) production. However, little information exists regarding the effect of testosterone on stem cell function. We hypothesized that: 1) endogenous or exogenous estrogen will enhance stem cell production of VEGF, and 2) endogenous or exogenous testosterone will inhibit BMSC VEGF production. BMSCs were collected from adult male, female, castrated male and ovariectomized female rats. 100,000 cells were incubated with testosterone (1nM, 10nM, or 100nM) or estrogen (0.15nM, 1.5nM, or 15nM) for 48 hrs. Cell supernatants were collected and VEGF was measured by ELISA. MSCs harvested from castrated males, normal females, and ovariectomized females produced more VEGF compared to normal males. Castration was associated with the highest level (1018+/-98.26pg/ml) of VEGF production by BMSCs, which was significantly more compared to VEGF production by BMSCs harvested from normal male and normal female animals. Exogenous testosterone significantly reduced VEGF production in BMSCs harvested from ovariectomized females in a dose-dependent manner. Exogenous estrogen did not alter BMSC VEGF production. These findings suggest that testosterone may work on BMSCs to decrease protective growth factor production, and effective removal of testosterone via castration may prove to be beneficial in terms of protective growth factor production. By manipulating the mechanisms that BMSCs use to produce growth factors, we may be able to engineer stem cells to produce maximum growth factors during therapeutic use.