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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 12 4765-4770
Copyright © 2000 by The Endocrine Society

Original Studies

Progesterone Enhances Interleukin-15 Production in Human Endometrial Stromal Cells in Vitro1

Hidetaka Okada, Tatsuya Nakajima, Mayumi Sanezumi, Akiko Ikuta, Katsuhiko Yasuda and Hideharu Kanzaki

Department of Obstetrics and Gynecology, Kansai Medical University, Moriguchi City, Osaka 570-8507, Japan

Address all correspondence and requests for reprints to: Hidetaka Okada, M.D., Department of Obstetrics and Gynecology, Kansai Medical University, Moriguchi City, Osaka 570-8507, Japan.

Interleukin-15 (IL-15) is a novel cytokine that stimulates lymphocyte proliferation and migration via a trimeric receptor sharing the ß and {gamma} signal-transducing chains with the IL-2 receptor. It is suggested that IL-15 is involved in regulating the proliferation and differentiation of uterine natural killer cells. In the human endometrium, we have recently reported that IL-15 messenger ribonucleic acid (mRNA) levels significantly increased during the secretory phase compared with those during the proliferative phase. In this study we investigated whether the female sex steroids progesterone (P) and estradiol (E2) regulate IL-15 messenger RNA (mRNA) and the secretion in human endometrial stromal cells (ESC) in vitro. Northern blot analyses revealed a significant increase in IL-15 mRNA levels in ESC treated with P alone or E2 plus P compared with vehicle. Furthermore, P is a potent inducer of IL-15 mRNA expression in ESC in a dose-dependent manner. On the other hand, E2 alone did not increase IL-15 mRNA expression. By enzyme-linked immunosorbent assay, IL-15 protein secretion was stimulated by P and further enhanced by combined treatment with E2 and P, whereas E2 alone was ineffective. It is suggested that IL-15 is deeply involved in the hormonal control of the human endometrium by P and E2.




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