In vitro metabolism of progesterone in the mammary tumor and the normal mammary gland of grs a mice and dependency of some steroid metabolizing enzyme activities on ovarian function

Mori, M.; Tamaoki B I.

European Journal of Cancer 16(2): 185-194


ISSN/ISBN: 0959-8049
Accession: 005649903

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[14C]Progesterone was incubated in vitro with cell-free homogenates of GRS/A mouse mammary tumor and normal mammary gland in the presence of NADPH. In the mammary tumor, 20.alpha.-hydroxy-4-pregnen-3-one, 5.alpha.-pregnane-3,20-dione, 20.alpha.-hydroxy-5.alpha.-pregnan-3-one, 3.alpha.-hydroxy-5.alpha.-pregnan-20-one, 5.alpha.-pregnane-3.alpha.,20.alpha.-diol and 4-pregnene-3.alpha.,20.alpha.-diol were identified as the metabolites. In the normal mammary gland, 20.alpha.-hydroxy-4-pregnen-3-one and 4-pregnene-3.alpha.,20.alpha.-diol were identified as the major metabolites, besides the 5.alpha.-reduced metabolites as minor ones. After establishment of the metabolic pathways of progesterone, 5.alpha.-reductase, and 3.alpha.- and 20.alpha.-hydroxysteroid dehydrogenases were suggested to be involved in the progesterone metabolism in these tissues. Activity of the 5.alpha.-reductase in the mammary tumor was higher than that in the normal mammary gland, but ovariectomy resulted in the reduction of this enzyme activity in the mammary tumor to the level of the normal mammary gland. By estradiol-17.beta.-benzoate administration to ovariectomized tumor-bearing animals, 5.alpha.-reductase activity was restored to the level of the mammary tumor of intact animals.