Metabolism of tritiated C19 steroids by shionogi mouse mammary tumors

In the present report, the metabolism of dehydroepiandrosterone, 5-androstene-3β, 17β-diol and androstenedione has been studied in two different Shionogi tumors, one is androgendependent (“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 3β-hydroxysteroid Δ⁵-Δ⁴ isomerase which causes the transformation of C₁₉ steroids into potent androgenic steroids. However, the androgen sensitive tumor is able to convert 5-androstene-3β, l7β-diol into 2-hydroxyestrogens while the rate of conversion is extremely low in the insensitive tumor. Most interestingly, the production of 5α-reduced steroids observed in both tissues was clearly higher in insensitive tumor homogenates.