Regulation of activin and inhibin in the adult testis and the evidence for functional roles in spermatogenesis and immunoregulation

Activin A provides a unique link between reproduction and immunity, which is especially significant in the adult testis. This cytokine, together with inhibin B and follistatin acting as regulators of activin A activity, is fundamentally involved in the regulation of spermatogenesis and testicular steroidogenesis. However, activin A also has a much broader role in control of inflammation, fibrosis and immunity. In the Sertoli cell, activin A is regulated by signalling pathways that normally regulate stress and inflammation, signalling pathways that intersect with the classical hormonal regulatory pathways mediated by FSH. Modulation of activin A production and activity during spermatogenesis is implicated in the fine control of the cycle of the seminiferous epithelium. The immunoregulatory properties of activin A also suggest that it may be involved in maintaining testicular immune privilege. Consequently, elevated activin A production within the testis during inflammation and infection may contribute to spermatogenic failure, fibrosis and testicular damage.