Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone

Although tumor necrosis factor-alpha (TNF alpha) has been shown mainly to i nhibit proliferation and induce apoptosis in a variety of cells, no informa tion is available regarding whether human leiomyoma cells express TNF alpha . In the present study, we examined the expression of TNF alpha in leiomyom as, in comparison with that in the adjacent normal myometrium, using immuno histochemical staining and Western immunoblot analysis with a polyclonal an tibody to human TNF alpha. Furthermore, we investigated the effect of sex s teroid hormones on TNF alpha expression in leiomyoma cells cultured under s erum-free, phenol red-free conditions. Immunohistochemical staining showed that TNF alpha expression in leiomyoma cells was higher than that in the ad jacent normal myometrial cells, being more abundant in the proliferative ph ase than in the secretory, progesterone (P4)-dominated, phase of the menstr ual cycle. TNF alpha expression in leiomyoma cells in pregnant uterus was s carce. Western immunoblot analyses of leiomyoma and normal myometrial tissu e extracts revealed that TNF alpha, with a molecular mass of 17.3 kDa, was abundantly present in leiomyoma tissue extracts, relative to normal myometr ial tissue extracts, and that TNF alpha expression in leiomyoma cells was m ost abundant in the proliferative phase of the menstrual cycle, less abunda nt in the secretory phase, and least abundant in pregnant uterus; whereas n o such changes in TNF alpha expression were noted in the normal myometrium. In monolayer cultures of uterine leiomyoma cells under serum-free conditio ns, addition of P4 (3.18 x 10(-7) mol/L) resulted in a decrease in TNFa exp ression in the cells, relative to that in control cultures, whereas treatme nt with 17 beta -estradiol (3.67 x 10(-8) mol/L) did not affect the TNF alp ha expression in the cells. The concentrations of sex steroids used were wi thin the physiological tissue concentrations noted in leiomyoma and myometr ium. The present results suggest that the abundant expression of TNF alpha may be a molecular basis characteristic of leiomyomas in the human uterus a nd that P4 may play a vital role in down-regulating the expression of TNF a lpha in human uterine leiomyoma.