Search

Abstract: The activins, as members of the transforming growth factor-β superfamily, are pleiotrophic regulators of cell development and function, including cells of the myeloid and lymphoid lineages. Clinical and animal studies have shown that activin levels increase in both acute and chronic inflammation, and are frequently indicators of disease severity. Moreover, inhibition of activin action can reduce inflammation, damage, fibrosis and morbidity/mortality in various disease models. Consequently, activin A and, more recently, activin B are emerging as important diagnostic tools and therapeutic targets in inflammatory and fibrotic diseases. Activin antagonists such as follistatin, an endogenous activin-binding protein, offer considerable promise as therapies in conditions as diverse as sepsis, liver fibrosis, acute lung injury, asthma, wound healing and ischaemia–reperfusion injury. [Copyright &y& Elsevier]

The role of the inhibins, activins and follistatins in testicular function are being more clearly defined following studies describing the cellular localisation of these proteins to the testis and the availability of specific assay systems enabling measurement of these proteins. Taken together with the results of targetted gene inactivation experiments, several concepts emerge. Inhibin B is predominantly produced by the Sertoli cell in many adult male mammals whereas there is a perinatal peak of inhibin A in the rat. In contrast, activin A has its highest concentrations in the immediate post-natal period during which it is involved in the developmental regulation of both germ cells and Sertoli cells being modulated by follistatin. Activin A levels are considerably lower in the adult testis but Sertoli cell production is stimulated by interleukin-1 and inhibited by FSH. Little is known about the production of activin B due to the absence of a suitable assay but the βB subunit mRNA is expressed in germ cells and Sertoli cells and is stage-dependent. This pattern of expression suggest that it may be involved in autocrine or paracrine actions within the seminiferous epithelium. [Copyright &y& Elsevier]