Metabolism of testosterone by GR mouse mammary tumors

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.