Regulation of prostate branching morphogenesis by activin A and follistatin

Ventral prostate development occurs by branching morphogenesis and is an an drogen-dependent process modulated by growth factors. Many growth factors h ave been implicated in branching morphogenesis including activins (dimers o f beta (A) and beta (B) subunits); activin A inhibited branching of lung an d kidney in vitro. Our aim was to examine the role of activins on prostatic development in vitro and their localization in vivo. Organ culture of day 0 rat ventral prostates for 6 days with activin A (+/- testosterone) inhibi ted prostatic branching and growth without increasing apoptosis. The activi n-binding protein follistatin increased branching in vitro in the absence ( but not presence) of testosterone, suggesting endogenous activins may reduc e prostatic branching morphogenesis. In vivo, inhibin subunit was not expre ssed until puberty, therefore inhibins (dimers of alpha and beta subunits) are not involved in prostatic development. Activin beta (A) was immunolocal ized to developing prostatic epithelium and mesenchymal aggregates at ducta l tips. Activin beta (B) immunoreactivity was weak during development, but was upregulated in prostatic epithelium during puberty. Activin receptors w ere expressed throughout the prostatic epithelium. Follistatin mRNA and pro tein were expressed throughout the prostatic epithelium. The in vitro evide nce that activin and follistatin have opposing effects on ductal branching suggests a role for activin as a negative regulator of prostatic ductal bra nching morphogenesis. (C) 2001 Academic Press.