Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 294, Issue 5, Pages R1498-R1503Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00897.2007
Keywords
sex; sex hormones; estrogen; castration; ovariectomy; androgens
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Funding
- NHLBI NIH HHS [K99/R00 HL 0876077-0, R01 HL 085595, F32 HL 085982] Funding Source: Medline
- NIGMS NIH HHS [R01 GM 070628] Funding Source: Medline
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Deleterious effects of endogenous and exogenous testosterone on mesenchymal stem cell VEGF production. Am J Physiol Regul Integr Comp Physiol 294: R1498-R1503, 2008. First published March 12, 2008; doi:10.1152/ajpregu.00897.2007.- Modulating the paracrine effects of bone marrow mesenchymal stem cells (BMSCs) 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. One hundred thousand cells were incubated with testosterone ( 1, 10, or 100 nM) or estrogen ( 0.15, 1.5, or 15 nM) for 48 h. Cell supernatants were collected, and VEGF was measured by ELISA. BMSCs harvested from castrated males, normal females, and ovariectomized females produced more VEGF compared with normal males. Castration was associated with the highest level ( 1,018 +/- 98.26 pg/ml) of VEGF production by BMSCs, which was significantly more than that produced 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 that effective removal of testosterone's deleterious effects via castration may prove to be beneficial in terms of protective 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.
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