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Effects of Estrogen on Cell Proliferation and Leukotriene Formation in Transformed Mouse Leydig Cells Cultured under Serum-free Conditions¹

The Third Department of Internal Medicine [K. N., S. K., M. K., B. S.] and The Second Department of Pathology [Y. N., K. M.], Osaka University Hospital, Fukushima-ku, Osaka 553, and The Department of Anesthesiology, Shiga University of Medical Science, Ohtsu-Shi, Shiga 520-21 [Y. N.], Japan

B-1 F cells from mouse Leydig cell tumor (T 124958-R) were maintained in serum-free culture. Estrogen enhanced the growth of the cells, and this growth was suppressed by antiestrogens such as 4-hydroxytamoxifen or TAT, a newly developed antiestrogen. Since the growth of B-1 F cells was recently found to be inhibited by the metabolites of arachidonic acid, we examined the relationship between this metabolism and the enhancement of cell growth by estrogen.

Among the modulators affecting the metabolism of arachidonic acid, 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone, an inhibitor of 5-lipoxygenase, reproducibly stimulated the growth of the cells, whereas the cyclooxygenase inhibitor indomethacin had only the marginal growth-stimulatory effects. Phorbol ester had no growth-modulating effect. 17ß-Estradiol and 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone had some additive effects especially in terms of restoration of antiestrogen-induced inhibition. Moreover, the inhibition of DNA synthesis elicited by the addition of arachidonic acid in concentrations of 0.05 to 0.5 µg/ml was partly blocked by estrogen. Analyses of extracts of media and cells by high-pressure liquid chromatography and radioimmunoassay showed that 17ß-estradiol inhibited the synthesis of leukotrienes B₄, C₄, D₄, and E₄ and this inhibition could be restored by antiestrogen.

These results suggest that the enhancement of B-1 F cell growth by estrogen is at least partly mediated through its ability to inhibit leukotriene synthesis.

¹ Supported in part by grants from the Ministry of Education, Tokyo, Japan, by a Research Grant for Adult Diseases, by the Osaka Cancer Research Fund, and by the Hirai Cancer Research Fund.

² To whom requests for reprints should be addressed.

Received 5/ 1/89. Revised 3/ 9/90.