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Submitted on November 29, 2005
Accepted on March 27, 2006
Department of Obstetrics and Gynecology and Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan
* To whom correspondence should be addressed. E-mail: yutakaos-tky{at}umin.ac.jp.
Adiponectin, a pleiotropic cytokine, exerts its effects via the specific receptors, Adipo R1 and Adipo R2. Whereas circulating adiponectin concentrations decrease in women with endometriosis and endometrial cancer, possible effects of adiponectin and the presence of the receptors in the endometrium have not been determined. In this study, we examined the expression of adiponectin receptors, Adipo R1 and Adipo R2 in the human endometrium, and assessed effects of adiponectin in the endometrial cells. Expression of Adipo R1 and Adipo R2 in the endometrial tissues was evaluated by real-time quantitative PCR, in situ hybridization, and Western blotting. The effects of adiponectin on phosphorylation of AMP-activate protein kinase (AMPK), a regulator of energy homeostasis, in cultured endometrial stromal cells (ESCs) and epithelial cells (EECs) were studied by Western blotting. The effects of adiponectin on IL-1
-induced secretion of IL-6, IL-8 and MCP-1 from cultured ESCs were determined using specific ELISAs. The expression of Adipo R1 and Adipo R2 was detected in the endometrium. The expression of both genes was increased in the mid-luteal phase, the period of embryo implantation. In situ hybridization revealed that both Adipo R1 and Adipo R2 appeared to be equally expressed in the epithelial cells and in the stromal cells. Adiponectin increased phosphorylation of AMPK in ESCs and EECs. Adiponectin decreased IL-1
-induced secretion of IL-6, IL-8 and MCP-1 from ESCs. These findings suggest that adiponectin exerts energy-homeostatic and anti-inflammatory effects in the endometrium, and these effects might be relevant to pathological and physiological endometrium-related events such as implantation and endometriosis.
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