title: Progression of mouse transformed leydig-cells from estrogen-sensitive to estrogen-insensitive growth phenotype concomitant with loss of leukotriene d-4 receptor.
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.
authors.affiliation: SHIGA UNIV MED SCI,DEPT ANESTHESIOL,OTSU,SHIGA 52021,JAPAN. OSAKA MED CTR MATERNAL & CHILD HLTH,OSAKA 59002,JAPAN. OSAKA UNIV HOSP,DEPT INTERNAL MED 3,SUITA,OSAKA 565,JAPAN.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Terada
authors.forename: Y
authors.initials: Y
authors.lastname: Amakata
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: B
authors.initials: B
authors.lastname: Sato