Takemura Yuri, Osuga Yutaka, Yamauchi Toshimasa, Kobayashi Masaki, Harada Miyuki, Hirata Tetsuya, Morimoto Chieko, Hirota Yasushi, Yoshino Osamu, Koga Kaori, Yano Tetsu, Kadowaki Takashi, Taketani Yuji
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Endocrinology. 2006 Jul;147(7):3203-10. doi: 10.1210/en.2005-1510. Epub 2006 Apr 6.
Adiponectin, a pleiotropic cytokine, exerts its effects via the specific receptors AdipoR1 and AdipoR2. 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 AdipoR1 and AdipoR2 in the human endometrium and assessed effects of adiponectin in endometrial cells. Expression of AdipoR1 and AdipoR2 in endometrial tissues was evaluated by real-time quantitative PCR, in situ hybridization, and Western blotting. The effects of adiponectin on phosphorylation of AMP-activated protein kinase, 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-1beta-induced secretion of IL-6, IL-8, and monocyte chemoattractant protein 1 from cultured ESCs were determined using specific ELISAs. The expression of AdipoR1 and AdipoR2 was detected in the endometrium. The expression of both genes was increased in the midluteal phase, the period of embryo implantation. In situ hybridization revealed that both AdipoR1 and AdipoR2 appeared to be equally expressed in the epithelial cells and in the stromal cells. Adiponectin increased phosphorylation of AMP-activated protein kinase in ESCs and EECs. Adiponectin decreased IL-1beta-induced secretion of IL-6, IL-8, and monocyte chemoattractant protein 1 from ESCs. These findings suggest that adiponectin exerts energy-homeostatic and antiinflammatory effects in the endometrium, and these effects might be relevant to pathological and physiological endometrium-related events such as implantation and endometriosis.
脂联素是一种多效细胞因子,通过特异性受体脂联素受体1(AdipoR1)和脂联素受体2(AdipoR2)发挥作用。虽然子宫内膜异位症和子宫内膜癌女性的循环脂联素浓度会降低,但脂联素的潜在作用以及子宫内膜中这些受体的存在情况尚未确定。在本研究中,我们检测了脂联素受体AdipoR1和AdipoR2在人子宫内膜中的表达,并评估了脂联素对子宫内膜细胞的影响。通过实时定量聚合酶链反应、原位杂交和蛋白质免疫印迹法评估AdipoR1和AdipoR2在子宫内膜组织中的表达。通过蛋白质免疫印迹法研究脂联素对能量稳态调节因子腺苷酸活化蛋白激酶(AMPK)磷酸化的影响,该激酶存在于培养的子宫内膜基质细胞(ESC)和上皮细胞(EEC)中。使用特异性酶联免疫吸附测定法确定脂联素对白细胞介素-1β(IL-1β)诱导的培养ESC中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和单核细胞趋化蛋白1分泌的影响。在子宫内膜中检测到AdipoR1和AdipoR2的表达。在黄体中期(胚胎着床期),这两个基因的表达均增加。原位杂交显示,AdipoR1和AdipoR2在上皮细胞和基质细胞中的表达似乎相同。脂联素增加了ESC和EEC中AMPK的磷酸化。脂联素减少了IL-1β诱导的ESC中IL-6、IL-8和单核细胞趋化蛋白1的分泌。这些发现表明,脂联素在子宫内膜中发挥能量稳态和抗炎作用,这些作用可能与着床和子宫内膜异位症等与子宫内膜相关的病理和生理事件有关。