Formation of 5 alpha-products as major C19-steroids in estrogen-responsive mouse Leydig cell tumor lines.
Homogenates of estrogen-responsive mouse Leydig cell tumors (T 124958-R and T 22137) or 28- and 120-day-old mouse testes were incubated with [3H]progesterone or [14C]4-androstene-3,17-dione in the presence of NADPH, and progesterone metabolism and enzyme activities were estimated. The growth of T 124958-R tumor transplanted in BALB/c mice was markedly stimulated by estrogenization of host mice, but the growth of T 22137 tumor was evidently suppressed by the estrogenization. The major C21-17-OH-steroids and C19-steroids formed from progesterone by both tumors and the testes of immature mice were 5 alpha-steroids, such as 3 alpha,17-dihydroxy-5 alpha-pregnan-20-one, 5 alpha-androstane-3,17-dione, androsterone, 3 beta-hydroxy-5 alpha-androstan-17-one and 5 alpha-androstane-3 alpha,17 beta-diol. In contrast, the major steroids formed by the testes of adult mice were testosterone and 4-androstene-3,17-dione, and no or little 5 alpha-steroids were produced. 5 alpha-Reductase activities in both tumor cells (40-50 nmol/l X 10(8) cells per h) were also found to be approx. 5-6 times higher than that in Leydig cells of adult mouse testes (8 nmol/l X 10(8) Leydig cells per h), though 17-hydroxylase activity was much higher in the Leydig cells of adult testes (730 nmol/l X 10(8) Leydig cells per h) than in both tumor cells (1-7 nmol/l X 10(8) cells per h). Furthermore, the presence of significant amounts of endogenous androsterone and/or 5 alpha-androstane-3 alpha,17 beta-diol was demonstrated in both tumors by radioimmunoassay. The present results demonstrate for the first time that C19-5 alpha-steroids are major C19-steroid products (immature type of testicular androgen production) in Leydig cell tumor lines.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis*; D015113:Androstane-3,17-diol / Q000032:analysis; D000735:Androstenedione / Q000378:metabolism*; D000738:Androsterone / Q000378:metabolism; D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D007984:Leydig Cell Tumor / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011374:Progesterone / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000032:analysis; D013736:Testicular Neoplasms / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D004967:Estrogens; D015113:Androstane-3,17-diol; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D000738:Androsterone; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase