Postnatal Growth of Mouse Seminal Vesicle Is Dependent on 5α-Dihydrotestosterone*

Abstract

The seminal vesicles (SV) develop from the lower portion of the Wolffian ducts (WD) in response to androgens, which prevent their degeneration and subsequently stimulate organogenesis of the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. Earlier studies suggest that testosterone (T) is the active androgen for WD development. By contrast, development of urogenital sinus and external genitalia is dependent upon 5 alpha-dihydrotestosterone (DHT), produced by 5 alpha-reductase within the target tissue itself. To reevaluate the possible role of DHT during SV morphogenesis, SVs from 0-day-old (day of birth) mice were grown for 3, 6, or 9 days in either serum-free or serum-containing medium in the presence or absence of T (10(-7) M) or DHT (10(-8) M). The serum-free medium consisted of Ham's F-12-Dulbecco's Modified Eagle's Medium (1:1) containing insulin, transferrin, cholera toxin, BSA, and epidermal growth factor. The serum-containing medium was Ham's F-12-Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum. Epithelial branching morphogenesis of SVs occurred in serum-free or serum-containing medium supplemented with either T or DHT and was comparable to that of SVs of similar ages in vivo. In serum-containing medium the DNA content of the cultures was about 2-fold higher in T-containing vs. T-deficient medium. However, in serum-free medium the DNA content was the same in cultures grown with or without T. SVs cultured under serum-free conditions in the presence of T plus 390 MSD (17 beta-N,N-diisopropylcarbamoyl-4-aza-5 alpha-androstan-3-one, an inhibitor of 5 alpha-reductase) were completely inhibited in their development, while in the presence of DHT plus 390 MSD, branching morphogenesis was comparable to that in SVs cultured in the presence of T or DHT alone. In medium lacking either T or DHT, SV development was inhibited. In addition, it was confirmed by TLC that [1 beta,2 beta-3H]T was converted into [3H]DHT at the ratio of 15.4% for the first 2 days and at 35.3% for the subsequent 2 days of the culture of SVs in serum-free medium. These data demonstrate that T is important as a precursor of DHT and DHT is the major androgen in the postnatal development of mouse SVs from the lower WD.