Effects of flutamide and finasteride on rat testicular descent.
The endocrine control of descent of the testis in mammalian species is poorly understood. The androgen dependency of testicular descent was studied in the rat using an antiandrogen (flutamide) and an inhibitor of the enzyme 5 alpha-reductase (finasteride). Androgen receptor blockade inhibited testicular descent more effectively than inhibition of 5 alpha-reductase activity. Moreover, its inhibitory effect was limited to the outgrowth phase of the gubernaculum testis, particularly the earliest stages of outgrowth. Gubernacular size was also significantly reduced in fetuses exposed to flutamide during the outgrowth period. In contrast, androgen receptor blockade or 5 alpha-reductase inhibition applied after the initiation of gubernacular outgrowth or during the regression phase did not affect testicular descent. Successful inhibition of the development of epididymis and vas by prenatal flutamide did not correlate with ipsilateral testicular maldescent, suggesting that an intact epididymis is not required for descent of the testis. Plasma androgen assays confirmed significant inhibition of dihydrotestosterone formation in finasteride-treated rats. These data suggest that androgens, primarily testosterone, are required during the early phases of gubernacular outgrowth for subsequent successful completion of testicular descent.
James Buchanan Brady Foundation, Department of Surgery, New York Hospital/Cornell University Medical College, New York 10021.
J R
JR
Spencer
T
T
Torrado
R S
RS
Sanchez
E D
ED
Vaughan
J
J
Imperato-McGinley
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000502:physiology*; D000736:Androstenes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000008:administration & dosage / Q000494:pharmacology*; D003456:Cryptorchidism / Q000139:chemically induced; D013196:Dihydrotestosterone / Q000378:metabolism; D004822:Epididymis / Q000187:drug effects / Q000196:embryology; D005260:Female; D018120:Finasteride; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology*; D005865:Gestational Age; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects / Q000196:embryology*; D013739:Testosterone / Q000378:metabolism
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D000728:Androgens; D000736:Androstenes; D001378:Azasteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; D005485:Flutamide