Dataset Information

Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-? interactions with G protein-?i and caveolin I.

ABSTRACT:

Unlabelled

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-? (mER?). 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 mER?, and smaller amounts of mER? and GPR30. A combination of microarrays, immunoblots, and quantitative immunoassays demonstrated the expression of members of all ?, ?, and ? G protein classes in these cells. Use of selective inhibitors showed that the G(?i) subtype was the primary initiator of downstream ERK signaling. Using antibodies against the GTP-bound form of G(?) protein subtypes i and s, we showed that xenoestrogens (bisphenol A, nonylphenol) activated G(?i) at 15-30s; all alkylphenols examined subsequently suppressed activation by 5min. GTP-activation of G(?i) for all estrogens was enhanced by irreversible cumulative binding to GTP?S. In contrast, G(?s) was neither activated nor deactivated by these treatments with estrogens. ER? and G(?i) co-localized outside nuclei and could be immuno-captured together. Interactions of ER? with G(?i) and caveolin I were demonstrated by epitope proximity ligation assays. An ER?/? 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 ER? with G(?i) and caveolin I, but with some different characteristics, which could explain their disruptive actions.

SUBMITTER: Watson CS

PROVIDER: S-EPMC3304022 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Estrogen- and xenoestrogen-induced ERK signaling in pituitary tumor cells involves estrogen receptor-α interactions with G protein-αi and caveolin I.

Watson Cheryl S CS Jeng Yow-Jiun YJ Hu Guangzhen G Wozniak Ann A Bulayeva Nataliya N Guptarak Jutatip J

Steroids 20111230 5

<h4>Unlabelled</h4>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 comb ...[more]

PMID: 22230296

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