Androgens lower prostaglandin E2 levels in neonatal mouse bulbourethral gland in in vitro cultures.
The neonatal mouse bulbourethral gland (BUG) in vitro culture model is useful to study hormone-induced genitourinary (GU) tract growth and differentiation. Like the prostate, the BUG is a derivative of the urogenital sinus and may have relevance to understanding growth processes involved in normal and pathological GU tract development. Previous studies have reported androgen-induced elevation of prostaglandin E2 (PgE2) levels in mouse GU tract in vivo. PgE2 has been proposed to mediate neonatal GU tract masculinization. In our studies, tissues were obtained from neonatal male mice and cultured in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (1:1) supplemented with varying concentrations of androgen. PgE2 levels were measured by RIA in the medium, and tissue specimens were cultured for 7 days or less. During this period, androgens induced proliferation and glandular morphogenesis in the BUGs. In the absence of androgen, tissue and medium PgE2 levels increased over 7 days. Significant (P < 0.05) PgE2 increases over day 1 control values were observed from days 5-7 in tissues and on day 7 in media. During this same time period, androgen supplementation decreased PgE2 levels. Significant (P < 0.05) PgE2 decreases from day 1 cultures were observed from days 3-7 in tissues and on day 7 in media. PgE2 was decreased significantly (P < 0.05) by androgen compared to control values from days 3-7 in tissues and from days 5-7 in media. On day 7 of culture, PgE2 levels were significantly (P < 0.05) inhibited by androgen in a concentration-dependent fashion in tissues and media. Maximal androgen-induced inhibition of PgE2 levels was 96% and 99% in tissues and media, respectively. Although the addition of indomethacin to control cultures markedly inhibited PgE2 production, BUG morphology was unaffected. In addition, the morphology of androgen-stimulated BUGs does not appear to be affected by the addition of exogenous PgE2. We conclude that although androgens induce development and decrease PgE2 levels, PgE2 does not appear to play a major role in in vitro BUG postnatal growth and morphogenesis. The BUG in vitro culture model may mimic growth and morphogenetic processes occurring in the human GU tract. Further understanding of the role of steroid hormones and PG metabolism may yield additional insight into developmental and proliferative GU tract disorders.
Little
J S
JS
Department of Urology, Indiana University School of Medicine, Indianapolis 46223.
Best
K L
KL
Goode
R L
RL
Toomey
R E
RE
Neubauer
B L
BL
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002030:Bulbourethral Glands / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D017373:Cyproterone Acetate / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques
D000728:Androgens; D017373:Cyproterone Acetate; D015232:Dinoprostone; D007213:Indomethacin