Role of Glucocorticoids and cAMP-Mediated Repression in Limiting Corticotropin-Releasing Hormone Transcription during Stress
Autor: | Greti Aguilera, Paolo Sassone-Corsi, Ying Liu, Jack D. Shepard |
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Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
Rok vydání: | 2005 |
Předmět: |
Male
Time Factors Transcription Genetic Corticotropin-Releasing Hormone Response element Electrophoretic Mobility Shift Assay RNA polymerase II MESH: Rats Sprague-Dawley Rats Sprague-Dawley Corticotropin-releasing hormone 0302 clinical medicine Adrenal Cortex Hormones Transcription (biology) MESH: Animals In Situ Hybridization MESH: Adrenalectomy MESH: Chromatin Immunoprecipitation 0303 health sciences General Neuroscience Adrenalectomy MESH: Restraint Physical MESH: Gene Expression Regulation MESH: Corticotropin-Releasing Hormone MESH: RNA Heterogeneous Nuclear hormones hormone substitutes and hormone antagonists Glucocorticoid Cellular/Molecular medicine.drug Restraint Physical Chromatin Immunoprecipitation endocrine system medicine.medical_specialty MESH: Rats Blotting Western Repressor MESH: Stress In situ hybridization Biology MESH: Cyclic AMP Response Element Modulator Cyclic AMP Response Element Modulator MESH: Adrenal Cortex Hormones 03 medical and health sciences MESH: In Situ Hybridization Stress Physiological MESH: Analysis of Variance Internal medicine medicine Animals MESH: Blotting Western Electrophoretic mobility shift assay RNA Messenger Glucocorticoids MESH: RNA Messenger 030304 developmental biology Analysis of Variance MESH: Transcription Genetic MESH: Time Factors [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology MESH: Male Rats Endocrinology Gene Expression Regulation nervous system MESH: Electrophoretic Mobility Shift Assay biology.protein RNA Heterogeneous Nuclear MESH: Glucocorticoids MESH: Paraventricular Hypothalamic Nucleus 030217 neurology & neurosurgery Paraventricular Hypothalamic Nucleus |
Zdroj: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2005, 25 (16), pp.4073-81. ⟨10.1523/JNEUROSCI.0122-05.2005⟩ |
ISSN: | 1529-2401 0270-6474 |
DOI: | 10.1523/jneurosci.0122-05.2005 |
Popis: | The role of glucocorticoids and the repressor isoform of cAMP response element (CRE) modulator (CREM), inducible cAMP early repressor (ICER), in limiting corticotropin-releasing hormone (CRH) transcription during restraint stress were examined in both intact and adrenalectomized rats receiving glucocorticoid replacement. CRH primary transcript, measured by intronicin situhybridization, increased after 30 min of restraint and returned to basal levels by 90 min, despite the persistent stressor. The decline was independent of circulating glucocorticoids, because adrenalectomized rats displayed an identical pattern. ICER mRNA in the hypothalamic paraventricular nucleus (PVN) increased after 30 min and remained elevated for up to 4 h in a glucocorticoid-independent manner. Western blot and electrophoretic mobility shift assay analyses showed increases in endogenous ICER in the PVN of rats subjected to restraint stress for 3 h. Chromatin immunoprecipitation assays showed the recruitment of CREM by the CRH CRE in conjunction with decreases in RNA polymerase II (Pol II) binding in the PVN region of rats restrained for 3 h. These data show that stress-induced glucocorticoids do not mediate the limitation of CRH transcription. Furthermore, the ability of CREM to bind the CRH CRE and the time relationship between elevated CREM and reduced Pol II recruitment by the CRH promoter suggest that inhibitory isoforms of CREM induced during stress contribute to the decline in CRH gene transcription during persistent stimulation. |
Databáze: | OpenAIRE |
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