[Effects of androgen regulation system on bladder carcinogenesis in male mice].
OBJECTIVE
In several previous reports, it has been suggested that the androgen system is related to bladder carcinogenesis. In this study, to understand the mechanism underlying this relationship, we administered a LH-RH agonist depot (Leuprolide depot), a pure-antiandrogen (flutamide) or a 5 alpha-reductase inhibitor (finasteride) to the mice in the promotion state of bladder carcinogenesis by N-butul-N-(4-hydroxybutyl) nitrosamine (BBN).


METHODS
177 C3H/He male mice were divided into 7 groups. All mice were treated with 0.05% BBN for 10 weeks and were maintained over the subsequent 12 weeks with the following treatments. Group 1 was a control group; in group 2, castration was performed at the 11th week; in group 3, finasteride was administered starting the 11th week; in group 4, a LH-RH agonist depot was administered starting the 11th week; in group 5, flutamide was administered starting the 11th week; in group 6, both finasteride and a LH-RH agonist depot were administered simultaneously starting the 11th week; and in group 7, both flutamide and a LH-RH agonist depot were administered simultaneously starting the 11th week.


CONCLUSIONS
(1) We confirmed that castration significantly suppressed bladder carcinogenesis. (2) Finasteride or flutamide administration as monotherapy had no effect on the results; however, the dosages of these drugs may have been too low, so we are planning a study with higher doses. (3) Conversely, the LH-RH agonist depot significantly promoted bladder carcinogenesis, we believe that the high levels of testosterone immediately after the administration were responsible for this promotion. (4) Simultaneous administration of flutamide suppressed this LH-RH induced promotion of carcinogenesis.
Imada
S
S
Department of Urology, University of Tsukuba.
Akaza
H
H
Otani
M
M
Koiso
K
K
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D018120:Finasteride / Q000008:administration & dosage*; D005485:Flutamide / Q000008:administration & dosage*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D016729:Leuprolide / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009919:Orchiectomy; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D002085:Butylhydroxybutylnitrosamine; D018120:Finasteride; D005485:Flutamide; D016729:Leuprolide