17β-Estradiol Stimulates Resistin Gene Expression in 3T3-L1 Adipocytes via the Estrogen Receptor, Extracellularly Regulated Kinase, and CCAAT/Enhancer Binding Protein-α Pathways

Abstract

Resistin is known as an adipocyte-specific secretory hormone that can cause insulin resistance and decrease adipocyte differentiation. It can be regulated by sexual hormones, but the mechanism of estrogen's actions is still not clear. Using 3T3-L1 adipocytes, we found that 17 beta-estradiol (E2) up-regulated resistin mRNA expression in a dose- and time-dependent manner. The concentration of E2 that increased resistin mRNA levels by 100-250% was approximately 1 nM for a range of 1-24 h of treatment. Treatment with either actinomycin D or cycloheximide prevented E2-stimulated resistin mRNA expression, suggesting that the effect of E2 requires new mRNA and protein synthesis. Although E2 was shown to increase activities of the estrogen receptor (ER) and MAPK kinase 1 and the association of nuclear ER alpha and CCAAT/enhancer binding protein-alpha with the resistin gene promoter, signaling was demonstrated to be blocked by pretreatment with either ICI182780 or PD98059. Neither SB203580 nor LY294002 changed the E2-increased levels of resistin mRNA, but they respectively inhibited E2-stimulated phosphorylation of p38 MAPK and Akt. These results imply the ER alpha, ERK, and CCAAT/enhancer binding protein- are necessary for the E2 stimulation of transcription from the resistin promoter. Moreover, PD98059, but not SB203580 or LY294002, antagonized E2-increased resistin protein release. These data suggest that E2 likely modifies the distribution of the resistin protein between the intracellular and extracellular compartments via an ERK-dependent pathway.

Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer

“…In contrast, it includes the CCAAT/ enhancer-binding protein (C/EBP) element (Khanna -Gupta et al, 2005). C/EBP has been shown to associate with ER-a and the complex then acts as a transcription factor and can regulate gene promoter activity (Chen et al, 2006). This could explain why oestrogen induces MMP-8 production in HSC-3 cells.…”

Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways

“…3T3-L1 adipocytes (American Type Culture Collection, Manassas, VA) were obtained according to a previously published method (11), in which 2-day postconfluent 3T3-L1 preadipocytes (3 ϫ 10 6 cells on a 10-cm plate) were treated with DMEM containing a final concentration of 10 M dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine, and 10% FBS for 48 h. The medium was then changed to DMEM containing 10% FBS for an additional 6ϳ10 days. With this protocol, Ͼ90% adipocyte differentiation was achieved, as indicated by a phenotypical appearance and triglyceride accumulation (11). Differentiated adipocytes expressed 3.4-fold more resistin mRNA than did preadipocytes or differentiating preadipocytes.…”

“…For example, 17␤-estradiol (E 2 ) increased resistin gene expression and protein secretion of murine primary and secondary adipocytes, whereas ICI-182780, an estrogen receptor (ER) antagonist, prevented E 2 -stimulated resistin expression (11). The signal elements responsible for transducing the direct action of E 2 on resistin gene expression and secretion were found in 3T3-L1 adipocytes to include ER␣ and ERK (11).…”

“…Determining whether octylphenols have the same ability as the estrogen hormone in directly stimulating resistin gene expression and protein secretion by adipocytes (11) requires further investiga-tion. Octylphenols have been reported to stimulate cell proliferation and adipocyte formation in cultures of murine 3T3-L1 adipocytes, as indicated by an increase in the DNA content and by decreases in triglyceride content and lipoprotein lipase activity (28,29).…”

Adipose Tissue Metabolism and Effect of Postmenopausal Hormone Therapy on Change of Body Composition

“…Data on estrogen effects for resistin expression are limited. In a mouse adipocyte model, the regulatory effect of 17 -E2 on resistin expression is discordant [64,75]. Recently described novel adipokines, such as visfatin, retinol binding protein-4, and omentin, have been shown to exert some metabolic properties, but their biological actions linked to obesity and interactions with estrogen need to be elucidated.…”