Metabolism of tritiated C19 steroids by Shionogi mouse mammary tumors

In the present report, the metabolism of dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol and androstenedione has been studied in two different Shionogi tumors, one is androgen-dependent ("androgen sensitive") and grows in intact male mice and the other is apparently androgen-independent ("androgen insensitive") since the cells continue to grow in castrated antiandrogen (Flutamide) treated male animals. Our data clearly show that both the sensitive and insensitive tumors contain 3 beta-hydroxysteroid delta 5-delta 4 isomerase which causes the transformation of C19 steroids into potent androgenic steroids. However, the androgen sensitive tumor is able to convert 5-androstene-3 beta, 17 beta-diol into 2-hydroxyestrogens while the rate of conversion is extremely low in the insensitive tumor. Most interestingly, the production of 5 alpha-reduced steroids observed in both tissues was clearly higher in insensitive tumor homogenates.