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Journal of the Society for Gynecologic Investigation, Vol. 13, No. 8, 551-557 (2006)
DOI: 10.1016/j.jsgi.2006.09.004

Leptin Suppresses Human Chorionic Gonadotropin-Induced Cyclooxygenase-2 Expression and Prostaglandin Production in Cultured Human Granulose Luteal Cells

Eing-Mei Tsai, MD, PhD

Te-Fu Chan, MD

Yu Chang, MD

Po-Hui Chiang, MD, PhD

Chiao-Ya Chuang, MS

Cheng-Yu Long, MD

Cheen-Yin Chai, MD, PhD

Department of Obstetrics and Gynecology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Department of Obstetrics and Gynecology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC; and Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

Jau-Nan Lee, MD, PhD

Department of Obstetrics and Gynecology, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Department of Obstetrics and Gynecology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Department of Urology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC; and Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC tfchan{at}kmu.edu.tw

Objective: In a previous study, we demonstrated that high leptin levels at the time of human chorionic gonadotropin (hCG) injection impaired the pregnancy rate for women undergoing in vitro fertilization. In this study we examine leptin's effect on prostaglandin formation and cyclooxygenase (COX) expression induced by hCG in human granulose luteal (GL) cells.

Methods: Human GL cells were obtained from women undergoing ovarian hyperstimulation. COX expression and microsomal prostaglandin E synthase (mPGES) expression, as well as prostaglandin E2 (PGE2) and prostaglandin F2{alpha} (PGF2{alpha}) production were studied. This was done in both the presence and absence of leptin following hCG stimulation PGE2 and PGF2{alpha} were determined by enzyme-linked immunosorbent assay (ELISA). The expression of COX and mPGES were investigated by using immunocytochemical techniques in addition to Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.

Results: HCG and leptin do not affect COX-1 expression. However, leptin blocked COX-2 and mPGES expression induced by hCG. Moreover, while leptin, in various concentrations, did not affect PGE2 and PGF2{alpha} levels, it inhibited the elevation of PGE2 and PGF2{alpha} concentrations in response to hCG.

Conclusions: The study confirms that the expression of COX-2 is up-regulated by hCG in human GL cells. Leptin suppress hCG-induced PGE2 formation through the inhibition of COX-2 and mPGES expression. The preliminary results suggest a potential inhibiting effect of leptin on human GL cells induced by hCG.

Key Words: COX • granulosa-luteal cell • leptin • prostaglandin

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