CONICET | Buscador de Institutos y Recursos Humanos

In recent years dehydroepiandrostenedione (DHEA) has placed as an alternative therapy for hypoandrogenic conditions, promoting local synthesis of active steroids from this precursor, process that has been called intracrinology. In this study we compared vascular effects of DHEA and testosterone (T) in processes involved in vascular remodeling, like cell migration and proliferation in human umbilical vein endothelial cells (HUVEC) and endothelial production of PAI-1 and uPA, factors that regulate vascular remodeling. We demonstrated that PAI-1 expression was not affected by DHEA (2nM, 20nM and 200nM) while T induced a significant increase at all concentrations (0.1nM, 1nM and 10nM) at different treatment times, with a stimulation of 60?80% above control (p50.05). This T effect showed to be dependent of androgen receptor and independent of aromatization to estradiol. Regarding to uPA expression, 24h treatment with DHEA increased its expression (30% above controlp50.05) while with T treatment noeffect was observed in HUVEC cells. The effect of androgens on HUVEC proliferation (MTT assay) and cell migration (wound healing assay)were also studied. Time-response assays (12, 24, 36 and 48h) showed that both, T and DHEA, can stimulate cell growth (32% and 12% above control, 1nM T and 20nM DHEAp50.05). Both androgens promoted cell motility (262, 1664, 60611 control, 1nM T, 20nM DHEA migrating cells/field p50.01) with a higher effect of DHEA (3.7 times higher than T). The presented results suggest that DHEA exerts a more favorable effect in terms of vascular remodeling, decreasing PAI-1 expressionand stimulating uPA, these effects correspond to a higher stimulating action of DHEA on cell migration