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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., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Regulation of crucial events during spermatogenesis involves dynamic changes in cytokine production and interactions across the cycle of the seminiferous epithelium. Regulation of activin A and inhibin B production by the inflammatory cytokines, tumour necrosis factor α (TNFα) and interleukin 1α (IL1α), alone and in conjunction with FSH or a cAMP analogue (dibutyryl cAMP), was examined in cultures of Sertoli cells from 20-day old rats. Both TNFα and IL1α stimulated activin A secretion and expression of its subunit (β(A)) mRNA, and suppressed inhibin B secretion and expression of its subunit (α and β(B)) mRNAs. The actions of TNFα and IL1α were opposed by FSH and dibutyryl cAMP. Both cytokines inhibited FSH/dibutyryl cAMP-stimulated inhibin B secretion and mRNA expression as well as stem cell factor mRNA expression. Both cytokines also inhibited FSH-induced cAMP production, and reduced baseline FSH receptor mRNA expression. These data highlight the reciprocal relationship that exists between FSH/cAMP signalling and inflammatory cytokine signalling pathways in the control of Sertoli cell function, and production of activin A/inhibin B in particular. It is anticipated that these interactions play important roles in the fine control of events during the cycle of the seminiferous epithelium and in the inhibition of spermatogenesis during inflammation., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)

Bacterial lipopolysaccharide increased the production of interleukin 1alpha and activin A, and reduced production of inhibin B, in Sertoli cells from immature male rats measured by enzyme-linked immunosorbent assay (ELISA). The majority of immunoreactive interleukin 1alpha remained within the Sertoli cell, while both activin A and inhibin B were secreted. Lipopolysaccharide-stimulated expression of two interleukin 1alpha mRNA transcripts, measured by quantitative RT-PCR, but the levels of bioactive interleukin 1alpha in Sertoli cell extracts and medium, measured by in vitro bioassay, were comparatively low to undetectable. A specific antagonist of interleukin 1alpha had no effect on lipopolysaccharide-stimulated activin A or inhibin B responses. These data indicate that, in contrast to Sertoli cells from adult rats, lipopolysaccharide-induced regulation of activin A and inhibin B by prepubertal Sertoli cells does not involve secreted interleukin 1alpha. The data highlight the possibility of a role for intracellular interleukin 1alpha in the Sertoli cell response to inflammation, particularly in the immature testis.