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

Abstract

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 F_2α (PGF_2α) production were studied. This was done in both the presence and absence of leptin following hCG stimulation PGE₂ and PGF_2α 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 PGF_2α levels, it inhibited the elevation of PGE₂ and PGF_2α 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.

Keywords

COX granulosa-luteal cell leptin prostaglandin

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