Effects of estrogen receptor alpha and beta on the expression of visfatin and retinol-binding protein 4 in 3T3-L1 adipocytes

Abstract

The aim of this study was to investigate the effects of estrogen and estrogen receptor alpha (ER alpha) and beta (ER beta) 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 ER alpha agonist, 4,4',4 ''-(4-propyl[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), the ER beta agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), E2 with the ER alpha antagonist, 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride (MPP), and E2 with the ER beta 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 ER alpha 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 ER beta agonist or antagonist. The expression of visfatin was not affected by different concentrations of E2 and ERs. 17 beta-estradiol significantly increased the secretion of RBP4 and upregulated RBP4 expression via ER alpha but not ER beta in 3T3-L1 adipocytes. RBP4 expression was regulated by estrogen in the 3T3-L1 adipocytes and this effect was selectively mediated by ER alpha.