Steroid Δ⁴-Reductase Activity in Hepatomas of Different Growth Rates

The activities of steroid A⁴-5α-reductase and Δ⁴-5β-reductase were measured for 11 hepatomas of different growth rates and host livers. The A⁴-5α-reductase was determined in the microsomal fraction, and the Δ⁴-5β-reductase activity was measured in the 100, 000 x g supernatant fluid. Reduced Δ⁴-5α-and Δ⁴-5β-reductase activity was observed in the host liver of all animals bearing tumor in parallel with the increase in hepatoma growth rate. The decrease for both enzymes was quite similar and ranged from about 95% for the slow-growing hepatoma 44 to about 70% for the fast-growing hepatoma 42A. In the spectrum of hepatomas studied, the activities of both Δ⁴-5α-and Δ⁴-5β-reductase were significantly decreased in parallel with the increase in hepatoma growth rate. The decrease for A⁴-50-reductase ranged from 40% for the slow-growing hepatoma 44 to 8% for the fast-growing hepatoma 42A, while the decrease for A⁴-5a-reductase ranged from 3.8% for the slow-growing hepatoma 44 to 0.2% for the fast-growing hepatoma 42A. Stimulation of A⁴-5a-reductase activity with medroxyprogesterone acetate showed a 2-to 3-fold increase in enzyme activity in normal liver and host liver, but no effect was observed in hepatomas.