Several substances present in the environment, now classified as endocrine disruptors (EDs), strongly interfere with both androgen and estrogen actions in reproductive tissues. However, nowadays it is well recognized that these sex steroid hormones are more than regulators of gonadal functions. In fact, they, in synergy with genes, are responsible of sex-related differences in anatomical, physiological, and behavioral traits which characterize males and females of many vertebrate species, including humans. As an example, both androgens and estrogens are associated with muscle size and strength and significant sex-related differences have been described in muscle performance and regeneration. Thus, even if EDs are present in minute amount (part for trillion) in environment, their effects in male and female physiology could be greater than before expected also prejudicing the sex-steroid hormone-induced integrated physiological responses in women and men. Several mechanisms have been implicated in ED effects (e.g., DNA adduct formation, epigenetic modification, protein-interactions). Among others, the ability of EDs to impair hormone effects by binding to their receptors have been reported even if the putative presence of sex-related differences in susceptibility to EDs has not yet been elucidated.

Here, the action mechanisms of natural (i.e. the flavonoid naringenin) and synthetic (i.e., Bisphenol A) EDs in modulating sex steroid hormone receptor activities in muscle-derived cells will be discussed in order to define a possible sex hormone-related susceptibility to these compounds.