In vitro metabolism of progesterone in the mammary tumor and the normal mammary gland of GRS/A strain of mice and dependency of some steroid-metabolizing enzyme activities upon ovarian function

Mori, M.; Tamaoki, B.I.

European Journal of Cancer 16(2): 185-193


ISSN/ISBN: 0014-2964
PMID: 6929251
DOI: 10.1016/0014-2964(80)90150-4
Accession: 000907569

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[14C]Progesterone was incubated in vitro with cell-free homogenates of GRS/A mouse mammary tumour and normal mammary gland in the presence of NADPH. In mammary tumour, 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 normal mammary gland, 20 alpha -hydroxy-4-pregnen-3-one and 4-pregnene-3 alpha ,20 alpha -diol were identified as the major metabolites, 5 alpha -reduced metabolites being 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 progesterone metabolism in these tissues. Activity of 5 alpha -reductase in mammary tumour was higher than that in the normal mammary gland, but ovariectomy resulted in the reduction of this enzyme activity in the mammary tumour to the level in the normal mammary gland. By oestradiol-17 beta -benzoate administration to ovariectomized tumour-bearing animals, 5 alpha -reductase activity was restored to the level in mammary tumour of intact animals.