Inhibition of experimentally induced mouse prostatic hyperplasia by castration or steroid antagonist administration.
Mouse prostatic hyperplasia has been induced experimentally by implanting fetal urogenital sinus tissue into the prostate gland of syngeneic mice. We compared the effects of castration and steroid antagonist administration on the growth of the prostate gland during both the early (15 days) and late (30 days) phases of prostatic enlargement. Castration at the time of induction of prostatic hyperplasia is by far the most effective method of inhibiting prostatic overgrowth. A comparison of castration for 7 days with the short-term (7 days) administration of steroid antagonists showed that during the early phase of prostatic enlargement castration is more effective than antiandrogen, which is more effective than 5 alpha-reductase inhibitors. In the late phase of mouse prostatic enlargement, castration for 7 days is less effective than treatment with either antiandrogen or a 5 alpha-reductase inhibitor. Our data indicate that treatment with a combination of an antiestrogen (keoxifene) with a 5 alpha-reductase inhibitor (in particular, 6-methylene progesterone) is the most effective combination for reducing prostatic overgrowth. The antiestrogen (keoxifene) treatment alone was ineffective in both the early and late phases of prostatic overgrowth.
Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
R A
RA
Sikes
S
S
Thomsen
V
V
Petrow
B L
BL
Neubauer
L W
LW
Chung
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists / Q000627:therapeutic use; D000818:Animals; D001378:Azasteroids / Q000627:therapeutic use; D004247:DNA / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009919:Orchiectomy; D010880:Piperidines / Q000627:therapeutic use*; D011374:Progesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D020849:Raloxifene Hydrochloride; D014566:Urogenital System / Q000196:embryology / Q000502:physiology
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D001378:Azasteroids; D004965:Estrogen Antagonists; D010880:Piperidines; D013196:Dihydrotestosterone; C036790:6-methylene-4-pregnene-3,20-dione; D020849:Raloxifene Hydrochloride; D011374:Progesterone; C031563:17-N,N-diethylcarbamoyl-4-methyl-4-azaandrostane-3-one; D004247:DNA