Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes

Abstract Background The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in differen...

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Main Authors: Marcin Piechota, Michał Korostynski, Slawomir Golda, Joanna Ficek, Danuta Jantas, Ziolkowska Barbara, Ryszard Przewlocki
Format: Article
Language:English
Published: BMC 2017-04-01
Series:BMC Neuroscience
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Online Access:http://link.springer.com/article/10.1186/s12868-017-0352-5
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author Marcin Piechota
Michał Korostynski
Slawomir Golda
Joanna Ficek
Danuta Jantas
Ziolkowska Barbara
Ryszard Przewlocki
author_facet Marcin Piechota
Michał Korostynski
Slawomir Golda
Joanna Ficek
Danuta Jantas
Ziolkowska Barbara
Ryszard Przewlocki
author_sort Marcin Piechota
collection DOAJ
description Abstract Background The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in different types of neural cells is not yet fully understood. The aim of this study was to evaluate and compare transcriptional alterations induced by various steroid receptor agonists in primary cultures of astrocytes and neurons from mouse brain. Results We utilized whole-genome microarrays (Illumina Mouse WG-6) and quantitative PCR analyses to measure mRNA abundance levels. To stimulate gene expression we treated neuronal and astroglial cultures with dexamethasone (100 nM), aldosterone (200 nM), progesterone (200 nM), 5α-dihydrotestosterone (200 nM) and β-Estradiol (200 nM) for 4 h. Neurons were found to exhibit higher levels of expression of mineralocorticoid receptor, progesterone receptor and estrogen receptor 2 than astrocytes. However, higher mRNA level of glucocorticoid receptor mRNA was observed in astrocytes. We identified 956 genes regulated by steroids. In astrocytes we found 381 genes altered by dexamethasone and 19 altered by aldosterone. Functional classification of the regulated genes indicated their putative involvement in multiple aspects of cell metabolism (up-regulated Slc2a1, Pdk4 and Slc45a3) and the inflammatory response (down-regulated Ccl3, Il1b and Tnf). Progesterone, dihydrotestosterone and estradiol did not change gene expression in astrocytes. We found no significant changes in gene expression in neurons. Conclusions The obtained results indicate that glial cells might be the primary targets of transcriptional action of steroids in the central nervous system. Substantial changes in gene expression driven by the glucocorticoid receptor imply an important role for the hypothalamic–pituitary–adrenal axis in the hormone-dependent regulation of brain physiology. This is an in vitro study. Hence, the model may not accurately reflect all the effects of steroids on gene expression in neurons in vivo.
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spelling doaj.art-ab1be911328e4094b9418f844f5dee042022-12-22T02:26:51ZengBMCBMC Neuroscience1471-22022017-04-011811910.1186/s12868-017-0352-5Transcriptional signatures of steroid hormones in the striatal neurons and astrocytesMarcin Piechota0Michał Korostynski1Slawomir Golda2Joanna Ficek3Danuta Jantas4Ziolkowska Barbara5Ryszard Przewlocki6Department of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesDepartment of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesDepartment of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesDepartment of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesDepartment of Neuroendocrinology, Institute of Pharmacology Polish Academy of SciencesDepartment of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesDepartment of Molecular Neuropharmacology, Institute of Pharmacology Polish Academy of SciencesAbstract Background The mechanisms of steroids actions in the brain mainly involve the binding and nuclear translocation of specific cytoplasmic receptors. These receptors can act as transcription factors and regulate gene expression. However, steroid-dependent transcriptional regulation in different types of neural cells is not yet fully understood. The aim of this study was to evaluate and compare transcriptional alterations induced by various steroid receptor agonists in primary cultures of astrocytes and neurons from mouse brain. Results We utilized whole-genome microarrays (Illumina Mouse WG-6) and quantitative PCR analyses to measure mRNA abundance levels. To stimulate gene expression we treated neuronal and astroglial cultures with dexamethasone (100 nM), aldosterone (200 nM), progesterone (200 nM), 5α-dihydrotestosterone (200 nM) and β-Estradiol (200 nM) for 4 h. Neurons were found to exhibit higher levels of expression of mineralocorticoid receptor, progesterone receptor and estrogen receptor 2 than astrocytes. However, higher mRNA level of glucocorticoid receptor mRNA was observed in astrocytes. We identified 956 genes regulated by steroids. In astrocytes we found 381 genes altered by dexamethasone and 19 altered by aldosterone. Functional classification of the regulated genes indicated their putative involvement in multiple aspects of cell metabolism (up-regulated Slc2a1, Pdk4 and Slc45a3) and the inflammatory response (down-regulated Ccl3, Il1b and Tnf). Progesterone, dihydrotestosterone and estradiol did not change gene expression in astrocytes. We found no significant changes in gene expression in neurons. Conclusions The obtained results indicate that glial cells might be the primary targets of transcriptional action of steroids in the central nervous system. Substantial changes in gene expression driven by the glucocorticoid receptor imply an important role for the hypothalamic–pituitary–adrenal axis in the hormone-dependent regulation of brain physiology. This is an in vitro study. Hence, the model may not accurately reflect all the effects of steroids on gene expression in neurons in vivo.http://link.springer.com/article/10.1186/s12868-017-0352-5DexamethasoneAldosteroneFalse Discovery RateGlucocorticoid ReceptorMineralocorticoid Receptor
spellingShingle Marcin Piechota
Michał Korostynski
Slawomir Golda
Joanna Ficek
Danuta Jantas
Ziolkowska Barbara
Ryszard Przewlocki
Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
BMC Neuroscience
Dexamethasone
Aldosterone
False Discovery Rate
Glucocorticoid Receptor
Mineralocorticoid Receptor
title Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
title_full Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
title_fullStr Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
title_full_unstemmed Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
title_short Transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
title_sort transcriptional signatures of steroid hormones in the striatal neurons and astrocytes
topic Dexamethasone
Aldosterone
False Discovery Rate
Glucocorticoid Receptor
Mineralocorticoid Receptor
url http://link.springer.com/article/10.1186/s12868-017-0352-5
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AT danutajantas transcriptionalsignaturesofsteroidhormonesinthestriatalneuronsandastrocytes
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