Inhibin/activin and ovarian cancer

Inhibin and activin are members of the transforming growth factor beta (TGFbeta) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, alpha and either betaA or betaB (inhibin A and B). Activins are hetero- or homodimers of the beta-subunits. Inhibin and free alpha subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin alpha subunit gene deletion develop stromal/granulosa cell tumours suggesting that the alpha subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFbeta superfamily is also discussed.