Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Regulation and actions of the activins in adult testicular function (#162)

Mark Hedger 1
  1. MIMR-PHI Institute, Clayton, VIC, Australia

Activins belong to the transforming growth factor-β superfamily of cytokines, and play fundamental roles in the regulation of cell growth, differentiation and survival in a wide range of tissues. The biologically-active activins are dimers of the β-subunits of inhibin A and B, represented by activin A (βAβA), B (βBβB) and AB (βAβB). In the adult testis, activins are produced by several somatic cells, including the resident macrophages, Leydig cells and Sertoli cells. Spermatogenic cells express activin genes, but produce relatively little of the dimeric proteins. Regulation of activin A and, to a lesser extent, activin B, has been studied in some detail in the rat Sertoli cell. Activin A is produced in a cyclical pattern within the seminiferous epithelium, with a large peak of production immediately following the release of sperm by the Sertoli cell, when inhibin B levels are lowest. Activin A expression is stimulated via inflammation-related pathways mediated by the MAP kinases, JNK and p38 MAPK, activated by ligands of the Toll-like receptors, interleukin-1 and tumour necrosis factor. Activin A is suppressed by FSH and cAMP, so that activin A and inhibin B are produced by the Sertoli cell in a reciprocal manner. In contrast to activin A, activin B is not stimulated by inflammatory activation, and its production appears to be a passive process, being elevated in response to reduced inhibin B production. Activins are regulators of spermatogonial proliferation, meiotic progression and Sertoli tight junction integrity, and their cyclical expression pattern points to a key role in events within the cycle of the seminiferous epithelium, particularly around the time of spermiation. The ability of the activins to regulate the activity of immune cells also implicates these cytokines in control of the immune environment of the testis, through maintenance of immune privilege and responses to inflammation and infection.