The effect of the adrenal
steroids androst-5-ene-3 beta,17 beta-diol (delta 5-diol) and
androstenedione (delta 4-dione) was studied on the growth of mammary
carcinoma induced in the rat by dimethylbenz[a]
anthracene (DMBA). The plasma levels of the two
steroids were maintained at values within the range of those found in the circulation of post-menopausal women by constant release from osmotic pumps in ovariectomized animals. delta 5-diol and delta 4-dione, at the daily release rate of 500 micrograms, led to plasma levels of 1.26 +/- 0.19 and 1.72 +/- 0.75 ng/ml, respectively. At these physiologically relevant plasma concentrations, both delta 5-diol and delta 4-dione caused a marked stimulation of
tumor growth while having minimal or no effect on uterine weight or on plasma
prolactin and LH levels. Concomitant treatment with the
aromatase inhibitor aminoglutethimide completely blocked the stimulatory effect of delta 4-dione released from
silastic implants on
tumor growth, while simultaneous administration of the
antiandrogen flutamide had no significant effect. On the other hand, when
aminoglutethimide was administered with delta 5-diol, the stimulatory effect of the adrenal
steroid on
tumor growth was not affected. Such data indicate that, under the present experimental conditions, transformation of delta 4-dione into
androgens plays a minor role, the predominant effect of the adrenal
steroid being stimulation of
tumor growth through conversion into
estrogens, while delta 5-diol exerts a direct
estrogenic effect independent from
aromatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)