Anti-androgenic effects of Win 49,596 on development of the neonatal mouse bulbourethral gland in culture.
The effects of the anti-androgen Win 49,596, a steroidal androgen receptor antagonist, on the testosterone (T) dependent development of neonatal mouse bulbourethral glands (BUGs) were examined in vitro. Day of birth (day 0) BUGs were grown in organ culture for 6 days in Dulbecco's modified Eagle's medium:Ham's F-12 media (1:1, volume/volume) with 10% fetal calf serum. Cultures were grown with or without T (10 nM) and various concentrations of Win 49,596 (0-57.6 microns). The DNA content of BUGs grown with T alone increased 4-fold over the culture period and the epithelium grew and branched extensively; without T only minimal growth and epithelial morphogenesis occurred. In the presence of T, Win 49,596 inhibited development in a dose-dependent manner, with an ED50 of 0.8 microM; concentrations at or above 3.6 microM produced maximal inhibition of development. Win 49,596 alone at 14.4 microM did not stimulate BUG growth, demonstrating a lack of agonist activity. BUGs grown for 3 days with Win 49,596 and T, then an additional 6 days with only T, did not resume development. In summary, Win 49,596 produced a dose-dependent suppression of BUG development in vitro, and was not androgenic. Additionally, the inhibitory effects of Win 49,596 persist for at least 6 days following cessation of treatment.
Cooke
P S
PS
Department of Veterinary Biosciences, University of Illinois, Urbana 61801.
Reicherts
M R
MR
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D002030:Bulbourethral Glands / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D009924:Organ Culture Techniques; D011278:Pregnanes / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*
D000726:Androgen Antagonists; D011278:Pregnanes; D011720:Pyrazoles; D004247:DNA; C060492:zanoterone