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Relative potency of antiandrogens with reference to intracellular testosterone in the rat prostate
Author(s) -
Kondo Yasushi,
Homma Yukio,
Aso Yoshio,
Kawabe Kazuki,
Mieda Mamoru,
Takahashi Hiroo
Publication year - 1996
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(199609)29:3<146::aid-pros1>3.0.co;2-c
Subject(s) - antiandrogens , antiandrogen , cyproterone acetate , flutamide , endocrinology , medicine , potency , chlormadinone acetate , testosterone (patch) , prostate , cyproterone , androgen , chemistry , pharmacokinetics , pharmacology , population , prostate cancer , androgen receptor , hormone , biochemistry , cancer , in vitro , research methodology , environmental health
BACKGROUND Mechanisms of relative potency in direct action of antiandrogens have not been fully elucidated. METHOD Using castrated rats, the effects of antiandrogens on the prostatic weight gain induced by exogenous testosterone (T), and on T uptake into prostatic cells were examined. Tested antiandrogens were cyproterone acetate, chlormadinone acetate, a new steroidal antiandrogen, 17acetoxy‐6‐chloro‐2‐oxa‐4,6‐pregnadiene‐3,20‐dione (TZP‐4238), and one nonsteroidal type, flutamide (FL). RESULTS Suppression of prostatic weight gain, T uptake and serum concentrations of compounds, correlated well each other among steroidal antiandrogens, while FL was five times more active in suppressing weight gain than TZP‐4238, associated with a lower nuclear distribution of androgen. CONCLUSION The results suggest that 1) suppression of T uptake is a major and common mechanism of steroidal antiandrogens and the relative potency is attributable to pharmacokinetic characteristics in vivo, and 2) FL suppresses nuclear T uptake more specifically than steroidal antiandrogens. © 1996 Wiley‐Liss, Inc.