Endocrine Abstracts

Sex steroid hormone-induced variations of vascular smooth muscle cells (VSMCs) migration are critical in determining the sex/gender-related differences in male and female pathophysiology of cardiovascular system. Although several substances present in the environment, defined endocrine disruptors (EDs), could interfere with androgen and estrogen effects, the sex/gender-related susceptibility of VSMC motility to these substances is completely unknown. Here, naringenin (Nar) and bisphenol A (BPA) effects on male and female VSMC motility has been evaluated. VSMC motility was determined by Wound healing and cell migration assays. 17β-estradiol (E₂, 1–10 nM) induced a dose-dependent inhibition of motility in female-derived VSMC. In contrast, neither testosterone nor dihydrotestosterone (0.01–100 nM) modified male-derived VSMC motility. ERβ subtype-dependent activation of p38 was necessary for the E₂ effect on cell motility. High BPA concentration prevented E₂ effects in female-derived cells being without any effect in male-derived cells. Nar mimicked E₂ effects on female-derived cells even in the presence of E₂ or BPA or in male-derived VSMC. This latter effect was blocked by ERβ subtype inhibitor pre-treatment, but not by the AR inhibitor. These observations indicate that ERβ plays a pivotal role in vasculoprotection being the main receptor to mediate the effects of E₂ in the vascular wall. Moreover, although E₂ signals in VSMC are more susceptible to the impact of EDs than androgen signals, male-derived cells, expressing both ERs, possess a similar susceptibility to EDs than female-derived cells.