Regulation of Sertoli cell activin A and inhibin B by tumour necrosis factor α and interleukin 1α: Interaction with follicle-stimulating hormone/adenosine 3′,5′-cyclic phosphate signalling

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 (βA) mRNA, and suppressed inhibin B secretion and expression of its subunit (α and βB) 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.