Department of Obstetrics and Gynecology, Konyang University Hospital, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
Int J Mol Med. 2013 Sep;32(3):723-8. doi: 10.3892/ijmm.2013.1440. Epub 2013 Jul 12.
The aim of this study was to investigate the effects of estrogen and estrogen receptor α (ERα) and β (ERβ) on the expression of visfatin and retinol-binding protein 4 (RBP4) by treating 3T3-L1 adipocytes with estradiol (E2), estrogen receptor agonists and antagonists. Mature adipocytes were exposed to E2, the ERα agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), the ERβ agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), E2 with the ERα antagonist, 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP), and E2 with the ERβ antagonist, (5R, 11R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol [(R,R)-THC], at various concentrations. To determine the effects of ER subtypes on the expression of adipokines, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analyses were performed. E2 concentrations of 10-5 and 10-6 mol/l induced a statistically significant increase in the expression of RBP4 (P=0.012 and P=0.011, respectively). In the cells treated with 10-5 mol/l PPT, RBP4 expression significantly increased (P<0.05) in a dose-dependent manner. Treatment with the ERα antagonist, MPP (10-5 mol/l), and E2 suppressed the expression of RBP4 (P=0.032). However, the expression of RBP4 was not significantly altered when the cells were treated with the ERβ agonist or antagonist. The expression of visfatin was not affected by different concentrations of E2 and ERs. 17β-estradiol significantly increased the secretion of RBP4 and upregulated RBP4 expression via ERα but not ERβ in 3T3-L1 adipocytes. RBP4 expression was regulated by estrogen in the 3T3-L1 adipocytes and this effect was selectively mediated by ERα.
本研究旨在通过用雌二醇(E2)、雌激素受体激动剂和拮抗剂处理 3T3-L1 脂肪细胞,研究雌激素和雌激素受体 α(ERα)和 β(ERβ)对内脏脂肪素和视黄醇结合蛋白 4(RBP4)表达的影响。成熟脂肪细胞暴露于 E2、ERα 激动剂 4,4',4''-(4-丙基-[1H]-吡唑-1,3,5-三基)三苯酚(PPT)、ERβ 激动剂 2,3-双(4- 羟苯基)-丙腈(DPN)、E2 与 ERα 拮抗剂 1,3-双(4-羟苯基)-4-甲基-5-[4-(2-哌啶基乙氧基)苯酚]-1H-吡唑二盐酸盐(MPP)和 E2 与 ERβ 拮抗剂(5R,11R)-5,11-二乙基-5,6,11,12-四氢-2,8- 苊二醇[(R,R)-THC],在不同浓度下。为了确定 ER 亚型对脂肪因子表达的影响,进行了定量逆转录-聚合酶链反应(qRT-PCR)和 Western blot 分析。浓度为 10-5 和 10-6 mol/l 的 E2 诱导 RBP4 表达呈统计学显著增加(P=0.012 和 P=0.011)。在用 10-5 mol/l PPT 处理的细胞中,RBP4 表达呈剂量依赖性显著增加(P<0.05)。用 ERα 拮抗剂 MPP(10-5 mol/l)和 E2 处理抑制 RBP4 的表达(P=0.032)。然而,用 ERβ 激动剂或拮抗剂处理细胞时,RBP4 的表达没有明显改变。不同浓度的 E2 和 ERs 对内脏脂肪素的表达没有影响。17β-雌二醇通过 ERα显著增加 3T3-L1 脂肪细胞中 RBP4 的分泌并上调 RBP4 表达,但不通过 ERβ。在 3T3-L1 脂肪细胞中,RBP4 的表达受雌激素调节,这种作用是通过 ERα 选择性介导的。