Expression of adiponectin receptors and its possible implication in the human endometrium.
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.
Takemura
Yuri
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Yamauchi
Toshimasa
T
Kobayashi
Masaki
M
Harada
Miyuki
M
Hirata
Tetsuya
T
Morimoto
Chieko
C
Hirota
Yasushi
Y
Yoshino
Osamu
O
Koga
Kaori
K
Yano
Tetsu
T
Kadowaki
Takashi
T
Taketani
Yuji
Y
D055372:AMP-Activated Protein Kinases; D015153:Blotting, Western; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054419:Receptors, Adiponectin; D054390:Receptors, CCR2; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; C515334:CCR2 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D009097:Multienzyme Complexes; D054419:Receptors, Adiponectin; D054390:Receptors, CCR2; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases