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17β-estradiol modulates gene expression in the female mouse cerebral cortex.

Humphreys GI, Ziegler YS, Nardulli AM - PLoS ONE (2014)

Bottom Line: Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes.These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling.These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
17β-estradiol (E2) plays critical roles in a number of target tissues including the mammary gland, reproductive tract, bone, and brain. Although it is clear that E2 reduces inflammation and ischemia-induced damage in the cerebral cortex, the molecular mechanisms mediating the effects of E2 in this brain region are lacking. Thus, we examined the cortical transcriptome using a mouse model system. Female adult mice were ovariectomized and implanted with silastic tubing containing oil or E2. After 7 days, the cerebral cortices were dissected and RNA was isolated and analyzed using RNA-sequencing. Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes. These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling. E2 also altered the expression of genes linked to lipid synthesis and metabolism, vasoconstriction and vasodilation, cell-cell communication, and histone modification. These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment.

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E2 increases pERK protein levels.(A)Western blot analysis was used to monitor pERK and total ERK levels in the cortices of mice that had been treated with oil or E2 for 7 days. (B) pERK values were normalized to total ERK and are displayed as the normalized fold change ± SEM. The Student’s t-test was used to detect significant differences in oil- and E2- treated animals (*p<0.05). The number of animals in each treatment group is indicated at the base of each bar.
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pone-0111975-g004: E2 increases pERK protein levels.(A)Western blot analysis was used to monitor pERK and total ERK levels in the cortices of mice that had been treated with oil or E2 for 7 days. (B) pERK values were normalized to total ERK and are displayed as the normalized fold change ± SEM. The Student’s t-test was used to detect significant differences in oil- and E2- treated animals (*p<0.05). The number of animals in each treatment group is indicated at the base of each bar.

Mentions: The MAP kinase pathway plays a critical role in neuronal plasticity and survival [53] and E2 has been implicated in inducing rapid signaling through this pathway in neuroblastoma cells, primary cortical neurons, cortical explants, and the cerebral cortex in vivo [54], [69]–[71]. To determine whether MAP kinase signaling was activated after longer E2 treatment, we examined the level of phosphorylated extracellular regulated kinase (pERK) in the cortices of mice that had been treated with oil or E2 for 7 days. In fact, the level of pERK was significantly increased in the E2-treated animals (Fig. 4) demonstrating that E2 modulation of pERK and MAP kinase signaling is not limited to acute exposures (5–30 min), but is still enhanced after a longer treatment time.


17β-estradiol modulates gene expression in the female mouse cerebral cortex.

Humphreys GI, Ziegler YS, Nardulli AM - PLoS ONE (2014)

E2 increases pERK protein levels.(A)Western blot analysis was used to monitor pERK and total ERK levels in the cortices of mice that had been treated with oil or E2 for 7 days. (B) pERK values were normalized to total ERK and are displayed as the normalized fold change ± SEM. The Student’s t-test was used to detect significant differences in oil- and E2- treated animals (*p<0.05). The number of animals in each treatment group is indicated at the base of each bar.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221195&req=5

pone-0111975-g004: E2 increases pERK protein levels.(A)Western blot analysis was used to monitor pERK and total ERK levels in the cortices of mice that had been treated with oil or E2 for 7 days. (B) pERK values were normalized to total ERK and are displayed as the normalized fold change ± SEM. The Student’s t-test was used to detect significant differences in oil- and E2- treated animals (*p<0.05). The number of animals in each treatment group is indicated at the base of each bar.
Mentions: The MAP kinase pathway plays a critical role in neuronal plasticity and survival [53] and E2 has been implicated in inducing rapid signaling through this pathway in neuroblastoma cells, primary cortical neurons, cortical explants, and the cerebral cortex in vivo [54], [69]–[71]. To determine whether MAP kinase signaling was activated after longer E2 treatment, we examined the level of phosphorylated extracellular regulated kinase (pERK) in the cortices of mice that had been treated with oil or E2 for 7 days. In fact, the level of pERK was significantly increased in the E2-treated animals (Fig. 4) demonstrating that E2 modulation of pERK and MAP kinase signaling is not limited to acute exposures (5–30 min), but is still enhanced after a longer treatment time.

Bottom Line: Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes.These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling.These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

ABSTRACT
17β-estradiol (E2) plays critical roles in a number of target tissues including the mammary gland, reproductive tract, bone, and brain. Although it is clear that E2 reduces inflammation and ischemia-induced damage in the cerebral cortex, the molecular mechanisms mediating the effects of E2 in this brain region are lacking. Thus, we examined the cortical transcriptome using a mouse model system. Female adult mice were ovariectomized and implanted with silastic tubing containing oil or E2. After 7 days, the cerebral cortices were dissected and RNA was isolated and analyzed using RNA-sequencing. Analysis of the transcriptomes of control and E2-treated animals revealed that E2 treatment significantly altered the transcript levels of 88 genes. These genes were associated with long term synaptic potentiation, myelination, phosphoprotein phosphatase activity, mitogen activated protein kinase, and phosphatidylinositol 3-kinase signaling. E2 also altered the expression of genes linked to lipid synthesis and metabolism, vasoconstriction and vasodilation, cell-cell communication, and histone modification. These results demonstrate the far-reaching and diverse effects of E2 in the cerebral cortex and provide valuable insight to begin to understand cortical processes that may fluctuate in a dynamic hormonal environment.

Show MeSH
Related in: MedlinePlus