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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 5 2275-2280
Copyright © 2001 by The Endocrine Society

Original Studies

Tumor Necrosis Factor-{alpha} Expression in Human Uterine Leiomyoma and Its Down-Regulation by Progesterone1

Osamu Kurachi, Hiroya Matsuo, Takashi Samoto and Takeshi Maruo

Department of Obstetrics and Gynecology, Kobe University School of Medicine, Kobe 650-0017, Japan

Address all correspondence and requests for reprints to: Takeshi Maruo, M.D., Department of Obstetrics and Gynecology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: maruo{at}kobe-u.ac.jp

Although tumor necrosis factor-{alpha} (TNF{alpha}) has been shown mainly to inhibit proliferation and induce apoptosis in a variety of cells, no information is available regarding whether human leiomyoma cells express TNF{alpha}. In the present study, we examined the expression of TNF{alpha} in leiomyomas, in comparison with that in the adjacent normal myometrium, using immunohistochemical staining and Western immunoblot analysis with a polyclonal antibody to human TNF{alpha}. Furthermore, we investigated the effect of sex steroid hormones on TNF{alpha} expression in leiomyoma cells cultured under serum-free, phenol red-free conditions. Immunohistochemical staining showed that TNF{alpha} expression in leiomyoma cells was higher than that in the adjacent normal myometrial cells, being more abundant in the proliferative phase than in the secretory, progesterone (P4)-dominated, phase of the menstrual cycle. TNF{alpha} expression in leiomyoma cells in pregnant uterus was scarce. Western immunoblot analyses of leiomyoma and normal myometrial tissue extracts revealed that TNF{alpha}, with a molecular mass of 17.3 kDa, was abundantly present in leiomyoma tissue extracts, relative to normal myometrial tissue extracts, and that TNF{alpha} expression in leiomyoma cells was most abundant in the proliferative phase of the menstrual cycle, less abundant in the secretory phase, and least abundant in pregnant uterus; whereas no such changes in TNF{alpha} expression were noted in the normal myometrium. In monolayer cultures of uterine leiomyoma cells under serum-free conditions, addition of P4 (3.18 x 10-7 mol/L) resulted in a decrease in TNF{alpha} expression in the cells, relative to that in control cultures, whereas treatment with 17ß-estradiol (3.67 x 10-8 mol/L) did not affect the TNF{alpha} expression in the cells. The concentrations of sex steroids used were within the physiological tissue concentrations noted in leiomyoma and myometrium. The present results suggest that the abundant expression of TNF{alpha} may be a molecular basis characteristic of leiomyomas in the human uterus and that P4 may play a vital role in down-regulating the expression of TNF{alpha} in human uterine leiomyoma.




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