The metabolism of
testosterone by GR mouse mammary
tumors following serial
transplantation was studied. Oophorectomized female recipients were maintained on
estrone and
progesterone (OEP) or without
hormone maintenance (oophorectomized-only group) in order to assess whether the growth of the
tumor was
hormone dependent (HD) or
hormone independent (HI).
Tumors in the early generations of the OEP group were HD (generations 1 to 4), which became HI in the latter generations (G5 to G18). All
tumors developed in the oophorectomized-only group (generations 1 to 18) were HI. All
tumors investigated were capable of metabolizing
testosterone to 4-androstenedione,
16 alpha-hydroxytestosterone,
5 alpha-dihydrotestosterone,
5 alpha-androstanedione, and 5 alpha-androstanediol. Total 5 alpha-reduction in OEP group ranged between 50 and 60% of neutral metabolites in HD
tumors and dropped to 13 to 28% in HI
tumors (generations 5 to 18), similar to the activities (20 to 30%) of the HI
tumors in the oophorectomized only group. Different patterns of
estrogen synthesis were observed among these
tumors. Although
tumors showed the presence of appreciable amounts of
estriol,
estrone was synthesized only in 5 of the 9 HI
tumors in the oophorectomized only group. The most striking contrast was that
estradiol was synthesized by all HI
tumors in the oophorectomized-only group and the OEP group but not in the HD
tumors.