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Effects of androgen and antiandrogen treatment on canine prostatic arginine esterase
Author(s) -
Juniewicz P. E.,
Barbolt T. A.,
Egy M. A.,
Frenette G.,
Dube J. Y.,
Tremblay R. R.
Publication year - 1990
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/pros.2990170204
Subject(s) - antiandrogen , androgen , medicine , prostate , endocrinology , arginine , flutamide , urology , prostate cancer , androgen receptor , biology , biochemistry , hormone , cancer , amino acid
Abstract A series of experiments were conducted to investigate the regulation of the primary secretory protein of the canine prostate, arginine esterase, by androgens and/or new antiandrogens under development. In the first experiment, castration decreased ( P <0.05) prostatic arginine esterase levels relative to intact controls (0.26±0.1 and 17.0±0.1 μmole/min/mg protein, respectively). Treatment of castrate dogs with either 5, 10, or 20 silastic capsules (8 cm length) containing the androgen 5α‐androstane‐3α, 17β‐diol (3α‐diol) plus 1 capsule containing estradiol‐17β (E 2 ) or the i.m. injection of 25 mg 3α‐diol and 0.25 mg E 2 for 12 weeks resulted in a dose‐dependent increase ( P <0.05) in prostatic arginine esterase activity (6.8±1.7, 19.0±3.6, 21.3±0.9, and 14.2±0.7 μmole/min/mg protein, respectively). In the second experiment, steroid treatment (10 3α‐diol plus 1 E 2 silastic capsules) of castrate dogs for 12 weeks resulted in prostatic arginine esterase activity of 17.8±2.3 μmole/min/mg. Co‐administration of the steroidal androgen receptor antagonist Win 49,596 (WIN) at doses of 0.625, 2.5, 10, or 40 mg/kg/day p.o., dose‐dependently inhibited ( P <0.05) prostatic arginine esterase activity (14.9±1.1, 14.3±1.3, 3.4±1.9, and 0.21±0.1 μmole/min/mg, respectively) to levels similar to that observed in castrate controls (0.14±0.03 μmole/min/mg). Administration of the nonsteroidal androgen receptor antagonist flutamide at 10 mg/kg/day p.o. to steroid‐induced dogs also inhibited ( P <0.05) arginine esterase activity (0.07±0.02 μmole/min/mg). In the last experiment, treatment of intact dogs with WIN at 0.625, 2.5, 10, and 40 mg/kg/day for 16 weeks dose‐dependently reduced ( P <0.05) arginine esterase levels (17.0±1.0, 16.3±1.5, 10.2±1.2, and 3.9±2.5 μmole/min/mg, respectively) compared to intact controls (14.4±1.2 μmole/min/mg). Histomorphologic and ultrastructural evaluation of prostates from dogs indicated that antiandrogen treatment resulted in glandular epithelial atrophy as well as a reduction in the number of secretory granules. The results of these experiments support that canine prostatic arginine esterase activity is under androgenic control, can be inhibited by antiandrogen treatment and may serve as a functional marker of the androgenic state of the prostate. Whether the effects of androgen and antiandrogens on prostatic arginine esterase is direct or indirect due to a general inhibitory effect on secretory epithelial cell function requires additional study. Furthermore, subject to further evaluation, the steroidal androgen receptor antagonist, Win 49,596, may be useful in the treatment of androgen‐dependent disorders of the prostate.