Leptin promotes human endometrial carcinoma cell proliferation by enhancing aromatase (P450arom) expression and estradiol formation

ObjectiveLeptin, a multifunctional peptide hormone encoded by the obese (ob) gene, plays an important role in modulating lipid metabolism and energy equilibrium. Leptin reportedly acts as a cell growth factor and enhances the proliferation of various tumors. We investigated the effect of leptin on aromatase (P450arom) expression and estradiol (E2) formation in a model of endometrial carcinoma.Study designWe established a co-culture model of endometrial fibroblasts and the Ishikawa endometrial carcinoma cell line. P450arom mRNA and protein expression were measured with RT-PCR and immunoblotting, respectively, before and after leptin treatment. The effect of leptin on estradiol formation in endometrial carcinoma cells was also detected with a radioimmunological method.ResultsP450arom mRNA expression was increased in co-cultures treated with 100 ng/ml leptin (P < 0.01). Estradiol synthesis was induced when androstenedione was added to the culture medium, and significantly higher estradiol concentration was observed in co-cultures treated with 100 ng/ml leptin,ConclusionsLeptin is an important component of the microenvironment and stimulates endometrial carcinoma cell proliferation via enhancing P450arom expression and estradiol synthesis.