INHIBITORY EFFECTS OF RETINOIC ACIDS ON ANDROGEN-DEPENDENT DEVELOPMENT OF NEONATAL MOUSE SEMINAL-VESICLES IN-VITRO

The effects of retinoic acids (RAs) on development of seminal vesicles (SVs) of neonatal mice were investigated in vitro. SVs from 0-day-old male mice were cultured for 2-6 days in serum-free, chemically define d medium containing transferrin and BSA supplemented with 5 alpha-dihy drotestosterone (DHT; 10(-8) M) and insulin (10 mu g/ml), alone and in combination. Before culture, SVs from 0-day-old mice consisted of an unbranched epithelium surrounded by mesenchyme. SVs cultured in medium with DHT plus insulin or DHT alone formed numerous epithelial branche s after day 2 of culture, whereas epithelial branching did not occur i n SVs cultured with insulin alone. All-trans-RA or 13-cis-RA (10(-9)-1 0(-6) M) added to medium containing DHT plus insulin or DHT alone inhi bited epithelial branching in a dose-dependent manner. This inhibitory effect was reversible after removal of the retinoids from the medium on day 4 of culture. These RAs also decreased [H-3]thymidine labeling indexes of both epithelium and mesenchyme of SVs cultured in medium wi th DHT plus insulin or DHT alone and inhibited the increase in their p rotein contents. 9-Cis-RA was less inhibitory than all-trans-RA or 13- cis-RA on epithelial branching, [H-3]thymidine labeling indexes of epi thelium and mesenchyme, and protein content of SVs cultured in medium with DHT and insulin. In the absence of DHT (insulin alone), all-trans -RA did not affect either the [H-3]thymidine labeling indexes of epith elium and mesenchyme or the protein content of cultured SVs. Reverse t ranscriptase-PCR demonstrated strong expression of transcripts for mou se RA receptors (RAR alpha, RAR gamma, and RXR alpha), with lower leve ls of expression of RAR beta, RXR beta, and RXR gamma in neonatal SVs. The present results indicate that RAs reversibly inhibit androgen-dep endent development of neonatal mouse SVs, most likely through RARs.