Effect of metyrapone and aminoglutethimide on the murine sarcoma (MuSV‐M) and breast adenocarcinoma (C3HBA)

In previous studies with C3HBA tumors in C3H mice and with murine sarcoma virus tumors (MuSV‐M) in several varieties of mice, it was shown that administration of cortisone acetate or infliction of stressors that were presumed to cause increased secretion of adrenal glucocorticoids increased the severity of the tumor diseases. The administration of physiologic doses of estradiol did not influence the growth of these two tumors. We, however, had found that administration of metyrapone (MET) inhibits the growth of these tumors. We had attributed its action to 1) a decrease in corticosterone production and 2) an increase in 11 deoxycorticosterone production. To determine which of these factors was more important we compared the action of MET to aminoglutethimide (AG), since AG decreases both corticosterone and deoxycorticosterone levels. Experimental diets containing MET (200 mg/kg) or AG (120 mg/kg) were fed to CBA and C3H mice, starting three days prior to their inoculation with a 1 × 10 −1 and 1 × 10 −2 gr eq/ml concentration of MuSV‐M or 1 × 10 5 and 1 × 10 6 C3HBA cells, respectively. In the MuSV‐M system, MET lengthened the latency period of tumor development, inhibited tumor incidence, decreased tumor score, and shortened tumor regression time. In the C3HBA system, MET had a similar inhibiting effect on tumor growth. In contrast, AG had no statistically significant antitumor effect in either the MuSV‐M or C3HBA systems. We interpret these data as supporting the view that the antitumor effect of MET is due to an accumulation of deoxycorticosterone and a diminution of glucocorticoids because of the selective actions of MET on 11β‐steroid hydroxylase.