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Estrogen signaling in metabolic inflammation.

Monteiro R, Teixeira D, Calhau C - Mediators Inflamm. (2014)

Bottom Line: However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties.In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field.Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Medical Investigation Center, 4200-319 Porto, Portugal.

ABSTRACT
There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

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Related in: MedlinePlus

Estrogen signaling occurs through both genomic and nongenomic mechanisms. In classical, genomic, estrogen signaling ERs act as ligand-activated transcription factors, activating or repressing target genes within hours of ligand binding. ERs are located as monomers in the cytoplasm in protein complexes involving heat-shock proteins and estrogen binding promotes their dissociation from this complex and ER dimerization. ER dimers bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors. ERs also regulate gene expression in a ligand independent manner being activated downstream to growth factors binding to growth factor receptors, through the action of intracellular kinases or though the formation of heterodimers with different nuclear receptors (not shown). Genomic actions are modulated by cell-specific interaction with cofactors (coactivators or cosuppressors). Metabolic effects of estrogens seem to be largely mediated through nonnuclear ERs, either by interference with gene expression or by exerting nongenomic actions. This involves activation of ERs and G-protein-coupled ER located at the membrane or at extranuclear sites within seconds or minutes resulting in changes in Ca2+, K+, cAMP, and nitric oxide levels, activation of G protein-mediated events, and stimulation of different types of kinases such as extracellular-regulated kinases, phosphoinositide 3-kinases, mitogen-activated protein kinase, and c-Jun N-terminal kinases. E: estrogen; ER: estrogen receptor; ERE: estrogen-responsive element; ERK: extracellular-regulated kinase; GFR: growth factor receptor; GPER: G protein-coupled estrogen receptor; HSP: heat-shock protein; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; NO: nitric oxide; PI3K: phosphoinositide-3 kinase; TF: transcription factor.
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fig2: Estrogen signaling occurs through both genomic and nongenomic mechanisms. In classical, genomic, estrogen signaling ERs act as ligand-activated transcription factors, activating or repressing target genes within hours of ligand binding. ERs are located as monomers in the cytoplasm in protein complexes involving heat-shock proteins and estrogen binding promotes their dissociation from this complex and ER dimerization. ER dimers bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors. ERs also regulate gene expression in a ligand independent manner being activated downstream to growth factors binding to growth factor receptors, through the action of intracellular kinases or though the formation of heterodimers with different nuclear receptors (not shown). Genomic actions are modulated by cell-specific interaction with cofactors (coactivators or cosuppressors). Metabolic effects of estrogens seem to be largely mediated through nonnuclear ERs, either by interference with gene expression or by exerting nongenomic actions. This involves activation of ERs and G-protein-coupled ER located at the membrane or at extranuclear sites within seconds or minutes resulting in changes in Ca2+, K+, cAMP, and nitric oxide levels, activation of G protein-mediated events, and stimulation of different types of kinases such as extracellular-regulated kinases, phosphoinositide 3-kinases, mitogen-activated protein kinase, and c-Jun N-terminal kinases. E: estrogen; ER: estrogen receptor; ERE: estrogen-responsive element; ERK: extracellular-regulated kinase; GFR: growth factor receptor; GPER: G protein-coupled estrogen receptor; HSP: heat-shock protein; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; NO: nitric oxide; PI3K: phosphoinositide-3 kinase; TF: transcription factor.

Mentions: Estrogen signaling occurs through both genomic and nongenomic mechanisms summarized in Figure 2. Classical, genomic, estrogen signaling has been described to occur through specific nuclear receptors acting as ligand-activated transcription factors [12, 43], the estrogen receptors (ERs), of which two isomers are known: ERalpha and ERbeta [9, 44, 45]. ER distribution varies among tissues resulting in distinct effects of the hormone in different locations and the relative amount of each subtype may also change estrogen effects [9]. ERalpha is the predominant receptor in the kidney [43], heart [46], bone, uterus, liver, and AT [47], whereas ERbeta is the predominant receptor in the ovary, prostate, lung, bladder, hematopoietic cells, gastrointestinal tract, and central nervous system [43, 47].


Estrogen signaling in metabolic inflammation.

Monteiro R, Teixeira D, Calhau C - Mediators Inflamm. (2014)

Estrogen signaling occurs through both genomic and nongenomic mechanisms. In classical, genomic, estrogen signaling ERs act as ligand-activated transcription factors, activating or repressing target genes within hours of ligand binding. ERs are located as monomers in the cytoplasm in protein complexes involving heat-shock proteins and estrogen binding promotes their dissociation from this complex and ER dimerization. ER dimers bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors. ERs also regulate gene expression in a ligand independent manner being activated downstream to growth factors binding to growth factor receptors, through the action of intracellular kinases or though the formation of heterodimers with different nuclear receptors (not shown). Genomic actions are modulated by cell-specific interaction with cofactors (coactivators or cosuppressors). Metabolic effects of estrogens seem to be largely mediated through nonnuclear ERs, either by interference with gene expression or by exerting nongenomic actions. This involves activation of ERs and G-protein-coupled ER located at the membrane or at extranuclear sites within seconds or minutes resulting in changes in Ca2+, K+, cAMP, and nitric oxide levels, activation of G protein-mediated events, and stimulation of different types of kinases such as extracellular-regulated kinases, phosphoinositide 3-kinases, mitogen-activated protein kinase, and c-Jun N-terminal kinases. E: estrogen; ER: estrogen receptor; ERE: estrogen-responsive element; ERK: extracellular-regulated kinase; GFR: growth factor receptor; GPER: G protein-coupled estrogen receptor; HSP: heat-shock protein; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; NO: nitric oxide; PI3K: phosphoinositide-3 kinase; TF: transcription factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4226184&req=5

fig2: Estrogen signaling occurs through both genomic and nongenomic mechanisms. In classical, genomic, estrogen signaling ERs act as ligand-activated transcription factors, activating or repressing target genes within hours of ligand binding. ERs are located as monomers in the cytoplasm in protein complexes involving heat-shock proteins and estrogen binding promotes their dissociation from this complex and ER dimerization. ER dimers bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors. ERs also regulate gene expression in a ligand independent manner being activated downstream to growth factors binding to growth factor receptors, through the action of intracellular kinases or though the formation of heterodimers with different nuclear receptors (not shown). Genomic actions are modulated by cell-specific interaction with cofactors (coactivators or cosuppressors). Metabolic effects of estrogens seem to be largely mediated through nonnuclear ERs, either by interference with gene expression or by exerting nongenomic actions. This involves activation of ERs and G-protein-coupled ER located at the membrane or at extranuclear sites within seconds or minutes resulting in changes in Ca2+, K+, cAMP, and nitric oxide levels, activation of G protein-mediated events, and stimulation of different types of kinases such as extracellular-regulated kinases, phosphoinositide 3-kinases, mitogen-activated protein kinase, and c-Jun N-terminal kinases. E: estrogen; ER: estrogen receptor; ERE: estrogen-responsive element; ERK: extracellular-regulated kinase; GFR: growth factor receptor; GPER: G protein-coupled estrogen receptor; HSP: heat-shock protein; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; NO: nitric oxide; PI3K: phosphoinositide-3 kinase; TF: transcription factor.
Mentions: Estrogen signaling occurs through both genomic and nongenomic mechanisms summarized in Figure 2. Classical, genomic, estrogen signaling has been described to occur through specific nuclear receptors acting as ligand-activated transcription factors [12, 43], the estrogen receptors (ERs), of which two isomers are known: ERalpha and ERbeta [9, 44, 45]. ER distribution varies among tissues resulting in distinct effects of the hormone in different locations and the relative amount of each subtype may also change estrogen effects [9]. ERalpha is the predominant receptor in the kidney [43], heart [46], bone, uterus, liver, and AT [47], whereas ERbeta is the predominant receptor in the ovary, prostate, lung, bladder, hematopoietic cells, gastrointestinal tract, and central nervous system [43, 47].

Bottom Line: However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties.In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field.Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Medical Investigation Center, 4200-319 Porto, Portugal.

ABSTRACT
There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

Show MeSH
Related in: MedlinePlus