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Stimulative Effects of Estrogens on Tumor Growth and 5-Steroid Production in a Mouse Leydig Cell Tumor Line (T 124958-R)¹

Departments of Pathology [S. N., Y. N., D. T., K. M.] and Internal Medicine [B. S.], Osaka University Medical School, Kita-ku, Osaka 530, Japan

The effects of estrogens on the growth and enzyme activities for androgen synthesis in a mouse Leydig cell tumor line (T 124958-R) were studied. The s.c. implantation of a diethylstilbestrol pellet resulted in a marked enhancement of the tumor growth. 5-Reductase activity (nmol/g/h) in tumors rapidly grown in the presence of diethylstilbestrol pellet was 4 times higher than that in tumors slowly grown in the absence of diethylstilbestrol, whereas an inverse relation was found for 17ß-hydroxysteroid oxidoreductase activity. 17-Hydroxylase activities were similar in both tumors. The major C₂₁- and C₁₉-steroids formed from progesterone by the tumors grown in the presence of estrogen were 5-steroids such as 3- or 3ß-hydroxy-5-pregnan-20-one, 3,17-dihydroxy-5-pregnan-20-one, androsterone, and 5-androstane-3,17ß-diol, whereas the major steroids formed by the tumors in the absence of estrogen were 4-ene-3-ketosteroids such as 20-hydroxy-4-pregnen-3-one, 17-hydroxy-4-pregnene-3,20-dione, and testosterone. Furthermore, 10^-8 M of 17ß-estradiol added in serum-free medium for 10 days significantly enhanced 5-reductase activities per 10⁶ cells but significantly inhibited 17ß-hydroxysteroid oxidoreductase activity in primary cell culture. These results indicate that estrogens stimulate the growth of T 124958-R in vivo and that estrogens may directly enhance 5-reductase activity but inhibit 17ß-hydroxysteroid oxidoreductase activity in T 124958-R cells.

¹ Supported in part by a grant-in-aid for cancer research from the Ministry of Education, Science, and Culture and by the Ministry of Health and Welfare.

² To whom requests for reprints should be addressed.

Received 7/ 8/85. Revised 10/ 4/85. Accepted 10/10/85.