Antitumor and endocrine effects of an aromatase inhibitor (CGS 16949A) on DMBA-induced rat mammary tumor.
The antitumor and endocrine effects of a new nonsteroidal aromatase inhibitor were studied using DMBA-induced rat mammary carcinomas. CGS 16949A (CGS) was administered orally once daily for 3 weeks. A marked antitumor effect was noted at doses of more than 1 mg/kg, and weight gain was dose dependent. Histologic examination showed atrophic changes of the tumors and decreased expression of estrogen receptor levels. To investigate the mechanism of the antitumor effect of CGS, we studied the changes in endocrine function in rats given this agent. In the groups receiving more than 1 mg/kg of CGS, the serum estradiol and prolactin levels were lower and the serum luteinizing hormone level was higher than in the control group. In rats treated with CGS, ovary weight was increased, while uterus and pituitary weights were decreased. These changes were dose dependent. In contrast, the serum corticosterone level and adrenal weight remained unchanged. We conclude that CGS inhibits the growth of hormone-dependent tumors by changing the hormonal environment.
Houjou
T
T
First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.
Wada
T
T
Yasutomi
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002277:Carcinoma / Q000139:chemically induced / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D017316:Fadrozole / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D010902:Pituitary Gland / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects
D011960:Receptors, Estrogen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D011388:Prolactin; D007986:Luteinizing Hormone; D017316:Fadrozole