Effects of transforming growth factor beta-1 and all-trans-retinoic acid on androgen-induced development of neonatal mouse bulbourethral glands in vitro

Effects of transforming growth factor beta-1 (TGF-beta 1) and all-trans-ret inoic acid (All-trans-RA) on development of bulbourethral glands (BUGs) of neonatal mice were investigated in vitro. BUGs from 0-day-old male mice wer e cultured for 6 days in serum-free, chemically defined medium containing t ransferrin and bovine serum albumin, supplemented with 5 alpha-dihydrotesto sterone (DHT; 10(-8) M) and insulin (10 mu g/mL) alone or in combination. P rior to culture, BUGs from 0-day-old mice consisted of a simple epithelial rudiment encapsulated by mesenchyme. Epithelial growth and ductal branching occurred in BUGs cultured in medium containing DHT and insulin or DHT alon e, but epithelial branching did not occur in BUGs cultured in the presence of insulin alone. Addition of TGF-beta 1 at concentrations of > 5 ng/mL (0. 2 x 10(-9) M) to medium containing both insulin and DHT, inhibited the expe cted increase in overall size of BUGs, epithelial area and ductal branching in a dose-dependent manner. TGF-beta 1 also decreased [H-3]-thymidine labe lling indices of both epithelium and mesenchyme. TGF-beta 1 at 10 ng/mL eli cited these inhibitory effects on BUGs cultured in medium containing DHT al one. Addition of All-trans-RA (10(-8) to 10(-6) M) to the medium containing DHT plus insulin, or DHT alone did not exert significant effects on either overall size of BUGs or epithelial growth and ductal branching. All-trans- RA at 10(-6) M decreased the [H-3]-thymidine labelling index of mesenchyme of BUGs cultured in medium with DHT plus insulin or DHT alone, but did not decrease the [H-3]-thymidine labelling index of epithelium. The present res ults indicate that TGF-beta 1 inhibits androgen-induced epithelial and mese nchymal growth as well as epithelial morphogenesis of BUGs from neonatal mi ce. Such an inhibitory effect of TGF-beta 1 is not mimicked by All-trans-RA at physiological concentrations.