Inhibitory effect of androgens on DMBA-induced mammary carcinoma in the rat.
Constant release of the androgen 5 alpha-dihydrotestosterone (DHT) in ovariectomized rats bearing DMBA-induced mammary carcinoma caused a marked inhibition of tumor growth induced by 17 beta-estradiol (E2). That DHT acts through interaction with the androgen receptor is supported by the finding that simultaneous treatment with the antiandrogen Flutamide completely prevents DHT action. Particularly illustrative of the potent inhibitory effect of DHT on tumor growth are the decrease by DHT of the number of progressing tumors from 69.2% to 29.2% in E2-treated animals and the increase by DHT of the number of complete responses (disappearance of palpable tumors) from 11.5% to 33.3% in the same groups of animals. The number of new tumors appearing during the 28-day observation period in E2-treated animals decreased from 1.5 +/- 0.3 to 0.7 +/- 0.2 per rat during treatment with DHT, an effect which was also reversed by the antiandrogen Flutamide. The present data demonstrate, for the first time, that androgens are potent inhibitors of DMBA-induced mammary carcinoma growth by an action independent of inhibition of gonadotropin secretion, and suggest an action exerted directly at the tumor level.
Dauvois
S
S
MRC Group in Molecular Endocrinology, Laval University Medical Centre, Quebec, Canada.
Li
S M
SM
Martel
C
C
Labrie
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004343:Drug Implants; D004958:Estradiol / Q000097:blood; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D004343:Drug Implants; D013196:Dihydrotestosterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D005485:Flutamide