Dose-dependent hormonal induction of benign prostatic hyperplasia (BPH) in castrated dogs.
A model for the dose-dependent hormonal induction of benign prostatic hyperplasia (BPH) in castrated dogs has been established using subcutaneously implanted Silastic capsules containing 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) and estradiol-17 beta. In vivo release rates per capsule approximated 122.0 +/- 4.2 micrograms 3 alpha-diol and 22.7 +/- 0.8 micrograms estradiol per day based on in vitro studies and resulted in dose-dependent increases in serum 3 alpha-diol and dihydrotestosterone concentrations. The implantation of castrated dogs with either 10 or 20 Silastic capsules containing 3 alpha-diol and one capsule containing estradiol or the intramuscular injection of 3 alpha-diol (75 mg/week) and estradiol (0.75 mg/week) for 99 days significantly increased (P less than .01) prostatic weights and total prostatic DNA over intact controls. These treatments also resulted in a histomorphological pattern similar to that observed in dogs with the glandular form of spontaneous BPH. In addition, normal prostatic secretory function as determined by semen volume was maintained in these dogs. Although subcutaneous implantation of five Silastic capsules containing 3 alpha-diol and one capsule containing estradiol into castrated dogs resulted in prostatic weights and total prostatic DNA that were similar (P less than .10) to intact controls, these prostates were characterized histomorphologically by glandular atrophy and squamous metaplasia. Furthermore, prostatic secretory function was decreased (P less than .05) in these animals compared with intact controls at 3 months of treatment. This study has led to the development of a model of steroid-induced BPH that will facilitate the evaluation of competitive androgen-receptor antagonists in the dog.
Juniewicz
P E
PE
Department of Pharmacology, Sterling Research Group, Rensselaer, New York 12144.
Lemp
B M
BM
Barbolt
T A
TA
LaBrie
T K
TK
Batzold
F H
FH
Reel
J R
JR
D015113:Androstane-3,17-diol / Q000633:toxicity*; D000732:Androstanols / Q000633:toxicity*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D013196:Dihydrotestosterone / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000032:analysis / Q000633:toxicity*; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011470:Prostatic Hyperplasia / Q000139:chemically induced*; D012661:Semen / Q000032:analysis; D013739:Testosterone / Q000097:blood
D000732:Androstanols; D004343:Drug Implants; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D004958:Estradiol