Immunohistochemical localization of transforming growth factor-alpha and transforming growth factor-beta during early human fetal prostate development

Purpose: We investigated the role of peptide growth factors and androgens i n the developing human prostate. Materials and Methods: We performed immunohistochemical staining of prostat e tissue sections from human fetuses 9.5, 11.5, 13, 16.5, 18 and 20 weeks i n gestation. Results: The temporal and spatial expression of these growth factors was re lated to the gestational androgen surge. Before the androgen surge (9.5 to 11.5 weeks) transforming growth factor (TGF)-alpha, TGF-beta 1 and TGF-beta 3 but not TGF-beta 2 were present in the mesenchyme. The epithelium exhibi ted no detectable staining for any of the growth factors. During the androg en peak (13 to 16.5 weeks) TGF-beta 1 decreased and TGF-beta 2 increased in the mesenchyme, and TGF-alpha, TGF-beta 1 and TGF-beta 3 increased in the epithelium. With declining androgen levels TGF-alpha, TGF-beta 2 and TGF-be ta 3 remained unchanged but TGF-beta 1 increased in the mesenchyme with no change in the tested peptide growth factor levels in the epithelium. Conclusions: These data suggest that androgens regulate the differential ex pression of TGF-alpha and TGF-beta, and support a role for peptide growth f actors as the direct mediators of androgen action on the mesenchymal and ep ithelial interactions responsible for prostate development.