Inhibitory effects of transforming growth factor-beta 1 on androgen-induced development of neonatal mouse seminal vesicles in vitro.

Abstract

The effects of transforming growth factor-beta 1 (TGF beta 1) on the development of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured for 2-8 days in serum-free, chemically defined medium with or without 5 alpha-dihydrotestosterone (DHT) at 10(-8) M in the presence or absence of TGF beta 1. Before culture, SVs from 0-day-old mice had no epithelial branches. SVs cultured in medium with DHT formed numerous epithelial branches after day 2 of culture, whereas epithelial branching did not occur in SVs cultured without DHT. The addition of TGF beta 1 (10 ng/ml) to DHT-containing medium almost completely inhibited the formation of epithelial branches. However, the removal of TGF beta 1 from DHT-containing medium on day 2 or 4 of culture initiated the formation of epithelial branches. TGF beta 1 (10 ng/ml) decreased [3H]thymidine labeling indices of both epithelium and mesenchyme of SVs cultured in medium with DHT during 8 days of culture, an effect that was reversed after the removal of TGF beta 1 from the medium on day 2 or 4 of culture. In contrast, TGF beta 1 (10 ng/ml) did not affect the labeling indices of either epithelium or mesenchyme of SVs cultured in medium without DHT. TGF beta 1 (10 ng/ml) also suppressed the normal increase in protein and DNA contents of SVs cultured in medium with DHT, whereas it did not reduce protein or DNA contents of SVs cultured in medium without DHT. The present study indicates that androgen-dependent growth of the SV can be reversibly inhibited by TGF beta 1, whereas androgen-independent growth of the SV is insensitive to TGF beta 1.