PROGRESSION OF MOUSE TRANSFORMED LEYDIG-CELLS FROM ESTROGEN-SENSITIVE TO ESTROGEN-INSENSITIVE GROWTH PHENOTYPE CONCOMITANT WITH LOSS OF LEUKOTRIENE D-4 RECEPTOR
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- Published online on: November 1, 1994 https://doi.org/10.3892/ijo.5.5.1077
- Pages: 1077-1084
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Abstract
We have previously shown that growth enhancement of murine transformed Leydig cells (B-1F) by estrogen is partly mediated through inhibition of leukotriene formation due to suppression of 5-lipoxygenase activity; leukotrienes, which inhibit the proliferation of B-1F cells, play an important role in an autocrine loop for B-1F cells to proliferate in an estrogen-sensitive manner. An estrogen-insensitive cell line, termed Cl 4(-), was established from B-1F cells and maintained in serum-free culture medium without addition of estrogen. The proliferation of Cl 4(-) cells was not affected by the addition of 10(-11)-10(-6) M 17 beta-estradiol, whereas an estrogen receptor in Cl 4(-) cells appeared to be normal, as judged by its binding to estrogens. 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone (AA861), an inhibitor of 5-lipoxygenase, and indomethacin, a cyclooxygenase inhibitor, did not stimulate the proliferation of Cl 4(-) cells, while AA861 markedly stimulated the proliferation of B-1F cells. Analyses of extracts of medium and cells showed that estrogen and AA861 inhibited the production of leukotriene B-4, C-4, D-4 and E(4) in estrogen-insensitive Cl 4(-) cells as well as in estrogen-sensitive B-1F cells. We were able to demonstrate that no inhibition of the proliferation is observed in Cl 4(-) cells by addition of leukotriene D-4, which inhibited the proliferation of B-1F cells, and that the high affinity binding site for leukotriene D-4 is not present in Cl 4(-) whereas it is present in B-1F cells. These results suggest that the insensitivity of Cl 4(-) cell proliferation to estrogen is at least partly due to deficient binding of leukotriene D-4, since, in Cl 4(-) cells, estrogen inhibits the production of leukotriene D-4, which inhibits the proliferation of estrogen-sensitive parental cell line B-1F.