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Steroid Metabolism in the Normal Mammary Gland and in the Dimethylbenzanthracene-Induced Mammary Tumor of Rats^*

MAKOTO MORI, TAKESHI TOMINAGA and BUN-ICHI TAMAOKI

National Institute of Radiological Sciences (M.M. and B.T.), Anagawa-4-chome, Chiba-shi, 280, and Tokyo Metropolitan Komagome Hospital (T.T.), Honkomagome-3-chome Bunkyo-ku, Tokyo 113, Japan

Abstract

After incubation of [4-¹⁴C]progesterone with cell-free homogenates of 9,10-dimethyl-l, 2-benzanthracene (DMBA)-induced mammary tumor of rats, 20-hydroxy-4-pregnen-3-one, 5-pregnane-3,20-dione, 20-hydroxy-5-pregnan-3-one, 3-hydroxy-5-pregnan- 20-one, and 5-pregnane-3a,20-diol were identified as the metabolites. In normal mammary tissue, however, 4-pregnene-3a,20-diol was isolated in addition to 5areduced, and 3- and 20-hydroxy metabolites. When radioactive testosterone was employed as a substrate, 5-dihydrotestosterone and 5-androstane-3a,17β-diol were obtained as the metabolites of the mammary tumor. In the normal mammary gland, only 4-androstene- 3a,17β-diol was formed as its metabolite.

Although the enzyme activities relevant to the metabolism varied among the tumors examined, the activity of 20-hydroxysteroid dehydrogenase in the mammary tumor was significantly lower than that in the normal mammary gland, whereas the activity of 5areductase was higher in some of the mammary tumors than in the normal gland. The 5-reductase activity in the normal mammary gland was mostly localized in the crude microsomal fraction, whereas the same enzyme activity in the tumor was detected in all the organelle fractions. The activities of 20-hydroxysteroid dehydrogenase and NADPH-linked 3-hydroxysteroid dehydrogenase were found mainly in the cytosol fractions of the tumor and the normal tissue. The NADH-linked 3ahydroxysteroid dehydrogenase activity was detected only in the cytosol fraction of the normal mammary gland, but in the tumor studied, the activity of this enzyme was detected in all the subcellular fractions examined. (Endocrinology 102: 1387, 1978)

Footnotes

^* This work has been partly supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.

Visiting scientist from Department of Animal Breeding, Faculty of Agriculture, University of Tokyo, Tokyo 113, to National Institute of Radiological Sciences. To whom requests for reprints should be addressed at the National Institute of Radiological Sciences, 97ndash;1, 4-chome, Anagawa, Chiba-shi, Japan.

Received July 5, 1977.

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