The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer.
4-Hydroxy-f-androstene-3,17-dione (4-OH-A) when tested at various concentrations was found to inhibit markedly the conversion of 4-andorstene-3,17-dione to estrogens inhuman placental and rat ovarian microsomes. To obtain evidence that estrogen biosynthesis could also be reduced in vivo with 4-OH-A, rats were treated sc at a dose level of 50 mg/kg body weight. After 3 h the ovarian veins were cannulated and blood collected. Estradiol concentrations in the plasma were reduced by 80% compared to control values during the proestrous surge and on Day 4 of pregnancy. 4-OH-A was also found to be effective in controlling estrogen-dependent reproductive and neoplastic processes. In rats treated from Day 2-7 of pregnancy, implantation of fertilized ova was completely prevented in some rats, while in others either implantation was delayed or the development of implants was retarded. 4-OH-A treatment of rats having estrogen-dependent breast tumors induced by 7,12-dimethylbenz(a)anthracene caused 80% of the tumors to regress significantly in 4 weeks of treatment; 42% of these regressed completely.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D047072:Aromatase Inhibitors; D001835:Body Weight; D010064:Embryo Implantation / Q000187:drug effects*; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D011359:Proestrus; D051381:Rats
D047072:Aromatase Inhibitors; D004967:Estrogens; D000735:Androstenedione; D015127:9,10-Dimethyl-1,2-benzanthracene; C014594:formestane