Document Detail


Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-α interactions with G protein-αi and caveolin I.
MedLine Citation:
PMID:  22230296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple physiologic estrogens (estradiol, estriol, and estrone), as well as xenoestrogenic compounds (including alkylphenols and bisphenol A), can act via nongenomic signaling initiated by liganding of the plasma membrane estrogen receptor-α (mERα). We examined heterotrimeric G protein involvement leading to extracellular-regulated kinase (ERK) activation in GH3/B6/F10 rat anterior pituitary tumor cells that express abundant mERα, and smaller amounts of mERβ and GPR30. A combination of microarrays, immunoblots, and quantitative immunoassays demonstrated the expression of members of all α, β, and γ G protein classes in these cells. Use of selective inhibitors showed that the G(αi) subtype was the primary initiator of downstream ERK signaling. Using antibodies against the GTP-bound form of G(α) protein subtypes i and s, we showed that xenoestrogens (bisphenol A, nonylphenol) activated G(αi) at 15-30s; all alkylphenols examined subsequently suppressed activation by 5min. GTP-activation of G(αi) for all estrogens was enhanced by irreversible cumulative binding to GTPγS. In contrast, G(αs) was neither activated nor deactivated by these treatments with estrogens. ERα and G(αi) co-localized outside nuclei and could be immuno-captured together. Interactions of ERα with G(αi) and caveolin I were demonstrated by epitope proximity ligation assays. An ERα/β antagonist (ICI182780) and a selective disruptor of caveolar structures (nystatin) blocked estrogen-induced ERK activation. Conclusions: Xenoestrogens, like physiologic estrogens, can evoke downstream kinase signaling involving selective interactions of ERα with G(αi) and caveolin I, but with some different characteristics, which could explain their disruptive actions.
Authors:
Cheryl S Watson; Yow-Jiun Jeng; Guangzhen Hu; Ann Wozniak; Nataliya Bulayeva; Jutatip Guptarak
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-30
Journal Detail:
Title:  Steroids     Volume:  77     ISSN:  1878-5867     ISO Abbreviation:  Steroids     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-14     Completed Date:  2012-08-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0404536     Medline TA:  Steroids     Country:  United States    
Other Details:
Languages:  eng     Pagination:  424-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Dept. of Biochemistry & Molecular Biology, Univ. of Texas Medical Branch, Galveston, TX 77555-0645, USA. cswatson@utmb.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Caveolae / metabolism
Caveolin 1 / genetics,  metabolism*
Cell Line, Tumor
Cell Membrane / metabolism
Estrogen Receptor alpha / genetics,  metabolism*
Estrogens / pharmacology*
Estrogens, Non-Steroidal / pharmacology
Extracellular Signal-Regulated MAP Kinases / metabolism
GTP-Binding Protein alpha Subunits, Gi-Go / genetics,  metabolism*
Guanosine Triphosphate / metabolism
Immunoblotting
MAP Kinase Signaling System / drug effects*
Microscopy, Fluorescence
Oligonucleotide Array Sequence Analysis
Phenols / pharmacology*
Pituitary Neoplasms / genetics,  metabolism,  pathology
Protein Binding / drug effects
Rats
Grant Support
ID/Acronym/Agency:
R01 ES015292/ES/NIEHS NIH HHS; R01 ES015292-03/ES/NIEHS NIH HHS; R01 ES015292-04/ES/NIEHS NIH HHS; R01 ES015292-04S1/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Caveolin 1; 0/Estrogen Receptor alpha; 0/Estrogens; 0/Estrogens, Non-Steroidal; 0/Phenols; 25154-52-3/nonylphenol; 86-01-1/Guanosine Triphosphate; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go; MLT3645I99/bisphenol A
Comments/Corrections

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