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Altered Steroid ⁴-Reductase Activity in Mammary Tumor-bearing Rats¹

College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455

The effect of mammary tumors on steroid ⁴-reductase activity was investigated using in vitro and in vivo studies in three transplantable rat mammary tumors. Steroid ⁴-5-reductase activity was measured spectrophotometrically and was significantly decreased in the host livers from R3230AC and MT/W9a-B but was increased in 7,12-dimethylbenz(a)anthracene-induced No. 14 tumor-bearing rats. There were no significant alterations of 5ß-reductase activity in all animals investigated. In vivo studies using [¹⁴C]testosterone showed a similar pattern for saturation of the 4,5-double bond but that the more than doubled increase in 4,5-reduced metabolites observed in the in vivo studies in 7,12-dimethylbenz(a)anthracene-induced tumor-bearing rats cannot be explained by the increase observed in hepatic enzyme activity. Incubations with mammary tumor tissues showed that 7,12-dimethylbenz(a)anthracene-induced tumors have a very active ⁴-5-reductase enzyme which accounts for the observed increases in in vivo results. The surgical removal of the tumor abolishes the impairment in ⁴-reductase activity.

¹ These investigations were supported by Grant CA 22467 from the National Cancer Institute, USPHS.

Received 8/22/80. Accepted 1/12/81.