A role of inhibin as a tumor suppressor in Sertoli cells: down-regulation upon aging and repression by a viral oncogene

Inhibin, a member of the TGF-beta superfamily, is synthesized in the testis by Sertoli cells and exerts an endocrine regulatory function on pituitary hormone synthesis, A distinct local function has been proposed, negatively controlling cellular growth in the testis (tumor suppressor activity). A cr itical test for the identification of a tumor suppressor is the reversal of transformed growth properties upon re-expression of the gene in tumor-deri ved cell lines. Sertoli cell-derived tumoral lines were previously establis hed from tumors that develop in elderly transgenic males which express in t he testis the large T antigen of polyoma virus. Both the tumors and the cel ls in culture exhibited reduced levels of the inhibin alpha subunit mRNA, S table transfectants were generated, in which this subunit was expressed fro m a heterologous promoter. All of them exhibited a strict inhibition of gro wth at confluency, On the other hand, in addition to an aging-related decre ase in inhibin synthesis, the alpha subunit gene was down regulated in vivo in cells expressing the viral protein. The conjunction of these two factor s accounts for the age-related occurrence of testicular cancers in the tran sgenic model, again pointing to inhibin as a potent cell growth regulator i n the seminiferous epithelium.