Journal of the Society for Gynecologic Investigation

 

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Journal of the Society for Gynecologic Investigation, Vol. 11, No. 7, 457-464 (2004)
DOI: 10.1016/j.jsgi.2004.04.002

17ß-Estradiol Up-Regulates Prostacyclin Production in Cultured Human Uterine Myometrial Cells Via Augmentation of Both Cyclooxygenase-1 and Prostacyclin Synthase Expression

Daizo Korita, MD, DMSc

Hiroaki Itoh, MD, DMSc

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Norimasa Sagawa, MD, PhD

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan; fetus{at}kuhp.kyoto-u.ac.jp

Shigeo Yura, MD, PhD

Masahiro Yoshida, MD

Kazuyo Kakui, MD

Maki Takemura, MD

Shingo Fujii, MD, DMSc

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan

Objective: To investigate whether 17ß-estradiol elevates prostacyclin (PGI2) production in human myometrial cells in the middle of gestation.

Methods: The concentration of 6-keto-PGF1{alpha}, a stable metabolite of PGI2, in the culture medium was assessed using enzyme-linked immunosorbent assay (ELISA). Western blot analysis and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using TaqMan (Applied Biosystems, Foster City, CA) technology were performed to evaluate the expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), COX-2, and prostacyclin synthase (PGIS) in cultured human myometrial cells prepared from second trimester pregnant women (n = 3) after stimulation with 17ß-estradiol.

Results: Treatment with 17ß-estradiol (4-400 nM) dose-dependently elevated PGI2 secretion from cultured human myometrial cells. Western blot analysis detected cPLA2 and COX-1 and PGIS protein expression in the cultured human myometrial cells; however, COX-2 protein expression was below the detection sensitivity. Stimulation with 40-nM 17ß-estradiol significantly up-regulated protein and mRNA expression of both COX-1 and PGIS.

Conclusion: 17ßEstradiol from placenta may contribute to the augmentation of PGI2 production in the human myometrium in the middle of gestation via up-regulation of both COX-1 and PGIS expression.

Key Words: Estrogen • myometrium • pregnancy • prostacyclin • prostacyclin synthase


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