Requirements for estrogen receptor α membrane localization and function

Evinger, Albert J.; Levin, Ellis R.

doi:10.1016/j.steroids.2005.02.015

Cited by 101 publications

(63 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that non-genomic biological effects of resveratrol are mediated through membranebound subpopulations of ERa and ERb (Razandi et al 1999, Evinger & Levin 2005. However, in this study, ER blockers, TAM and ICI, did not reverse the inhibitory effects of resveratrol on 11b-HSD1 (Fig.…”

Section: Figurecontrasting

confidence: 47%

Resveratrol inhibits 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes

Tagawa¹,

Kubota²,

Kato³

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

It has been suggested that resveratrol, a polyphenol in wine, can regulate adiposity because it decreases adipose deposition in mice and rats; however, the mechanism underlying this effect has not been fully clarified. In humans and rodents, 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) is expressed in liver and adipose tissue. 11b-HSD1 converts inactive glucocorticoid into active glucocorticoid in adipocytes. Activated glucocorticoid plays an important role in the pathogenesis of central obesity. The objective of this study was to investigate the effects of resveratrol on 11b-HSD1 activity in rodent adipose tissue. 11b-HSD1 activity in microsomes from rat mesenteric adipose depots and 3T3-L1 adipocytes was determined in the presence of 11-dehydrocorticosterone with or without varying concentrations of resveratrol. Significant inhibition of 11b-HSD1 by resveratrol was observed in rat adipose microsomes and 3T3-L1 adipocytes within 10 min. Time-and dose-dependent effects were also observed. The 11b-HSD1 activity by resveratrol was also inhibited in rat epididymal adipose tissue, and this inhibition was not recovered by estrogen receptor blockers. The kinetic study revealed that resveratrol acted as a non-competitive inhibitor of 11b-HSD1. K i and IC 50 values of resveratrol were 39.6 and 35.2 mM respectively. Further, resveratrol did not affect the activities of 11b-HSD2 and hexose-6-phosphate dehydrogenase. These results suggest that the most likely mechanism of 11b-HSD1 inhibition by resveratrol is via interaction between resveratrol and 11b-HSD1 enzyme, rather than via a transcriptional pathway. We demonstrated that the antiobesity effects of resveratrol may partially be attributed to the inhibition of 11b-HSD1 activity in adipocytes.

show abstract

Section: Figurecontrasting

confidence: 47%

Resveratrol inhibits 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes

Tagawa¹,

Kubota²,

Kato³

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Synthesis of non-peptide hydrophobic drugs with similar competitive properties for ER (Rodriguez et al, 2004;Shao et al, 2004) is another approach to avoid this pitfall. (Cheskis, 2004;Singh and Kumar, 2005;Evinger and Levin, 2005;Kampa and Castanas, 2006). Studies aimed at knowing whether ERα17p also activates ER-mediated non-genomic responses are planned in the near future.…”

Section: Discussionmentioning

confidence: 99%

Calmodulin-independent, agonistic properties of a peptide containing the calmodulin binding site of estrogen receptor α

Gallo

Jacquemotte²,

Cleeren

et al. 2007

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

“…This P132L mutation leads to formation of misfolded caveolin-1 oligomers that are retained within the Golgi complex and are not targeted to caveolae on the plasma membrane (Lee et al 2002). Evinger and associates (Evinger & Levin 2005) have recently demonstrated that deletion of the caveolin-1 scaffolding domain (amino acid residues 60-100) largely prevents the localization of ERa at the plasma membrane. In the present study, we demonstrate a direct functional consequence of caveolin-1 overexpression in HEK-293 cells, i.e., caveolin-1 overexpression in the transfected HEK-293 cells induced caveolin-2 stabilization and expression and coordinately, significantly increased free cholesterol in the cell.…”

Section: Discussionmentioning

confidence: 99%

Association of estrogen receptor with plasma-membrane caveola components: implication in control of vitamin D receptor

Gilad

Schwartz

2007

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

This study was designed to provide a direct demonstration of the importance of caveolin-1 in the compartmentalization of estrogen receptor b (ERb) to the membrane, thus allowing 7b-estradiol (E2) to control vitamin D receptor (VDR) transcription and expression. Our strategy was to obtain cell lines expressing different levels of caveolin-1. To this end, we transfected human embryonic kidney 293 cells with a caveolin-1-expressing vector and obtained three cell-line variants: one expressing high amounts of caveolin-1 (clone A), one expressing low amounts of caveolin-1 (clone B), and one expressing high amounts of the nonfunctional P132L caveolin-1 mutant (clone C), and compared these with parental (wild-type, WT) cells expressing negligible levels of caveolin-1. In clone A, ERb colocalized to membrane preparations and E2 treatment induced significant ERK 1/2 phosphorylation and enhanced VDR expression. In clones B and C and the WT, ERb did not localize to membrane preparations and E2 treatment was ineffective at inducing VDR upregulation associated with ERK 1/2 phosphorylation. Luciferase reporter gene expression assays showed that the human VDR promoter is only highly responsive to E2 treatment in clone A, except in the presence of the ER-specific inhibitor ICI182 780. Cotransfection of clone A with the VDR promoter and several mutants of MAPK kinase (MEK) demonstrated that the constitutively active form of MEK significantly increases VDR promoter activation, while the catalytically inactive construct is ineffective in this regard. In clone A cells transfected with an activation protein-1 (AP-1)-luciferase construct, E2 significantly upregulated the promoter activity, while ICI182 780 completely eliminated this E2-mediated effect. Clone A cells transfected with a VDR promoter bearing a targeted mutation towards the AP-1 site showed reduced E2-mediated activation of luciferase activity. Taken together, our data confirm the importance of caveolin-1 in the association of ERb to the membrane caveolae, allowing ERK 1/2 phosphorylation and upregulation of VDR.

show abstract

Requirements for estrogen receptor α membrane localization and function

Cited by 101 publications

References 9 publications

Resveratrol inhibits 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes

Resveratrol inhibits 11β-hydroxysteroid dehydrogenase type 1 activity in rat adipose microsomes

Calmodulin-independent, agonistic properties of a peptide containing the calmodulin binding site of estrogen receptor α

Association of estrogen receptor with plasma-membrane caveola components: implication in control of vitamin D receptor

Contact Info

Product

Resources

About