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Steroid ⁴-Reductase Activity in Hepatomas of Different Growth Rates¹

College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455 [J. E. H., Y. J. A.], and Department of Biochemistry, Howard University College of Medicine, Washington, D. C. 20001 [H. P. M.]

The activities of steroid ⁴-5-reductase and ⁴-5ß-reductase were measured for 11 hepatomas of different growth rates and host livers. The ⁴-5-reductase was determined in the microsomal fraction, and the ⁴-5ß-reductase activity was measured in the 100,000 x g supernatant fluid.

Reduced ⁴-5- and ⁴-5ß-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 ⁴-5- and ⁴-5ß-reductase were significantly decreased in parallel with the increase in hepatoma growth rate. The decrease for ⁴-5ß-reductase ranged from 40% for the slow-growing hepatoma 44 to 8% for the fast-growing hepatoma 42A, while the decrease for ⁴-5- reductase ranged from 3.8% for the slow-growing hepatoma 44 to 0.2% for the fast-growing hepatoma 42A.

Stimulation of ⁴-5-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.

¹ This research was supported in part by a grant from the Graduate School, University of Minnesota and Minnesota Medical Foundation Grant 0694-5813.

² Recipient of USPHS Research Grant CA 10729 during the tenure of which a portion of this work was done.

³ To whom requests for reprints should be addressed, at the College of Pharmacy, University of Minnesota, Minneapolis, Minn. 55455.

Received 10/11/73. Accepted 1/21/74.