NF-κB Participates in the Corticotropin-releasing, Hormone-induced Regulation of the Pituitary Proopiomelanocortin Gene
Corticotropin-releasing hormone is a main regulator of mammalian stress response by stimulating pituitary proopiomelanocortin (POMC) gene expression, and thus adrenocorticotropic hormone (ACTH) secretion, which then causes glucocorticoid release from the adrenal. In a recent study in the pituitary c...
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Veröffentlicht in: | The Journal of biological chemistry 2004-03, Vol.279 (12), p.10837-10840 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | Corticotropin-releasing hormone is a main regulator of mammalian stress response by stimulating pituitary proopiomelanocortin (POMC) gene expression, and thus adrenocorticotropic hormone (ACTH) secretion, which then causes glucocorticoid release from the adrenal. In a recent study in the pituitary corticotroph cell line AtT20, oxidative stress stimulated the activity of nuclear transcription factor B (NF-κB), whereas corticotropin-releasing hormone (CRH) inhibited both the constitutive and the oxidative stress-induced NF-κB DNA-binding activity. To further investigate the role of NF-κB on the CRH-induced pituitary POMC gene activation, AtT20 cells were transiently transfected with a POMC-luciferase construct mutated at an NF-κB binding site. After treatment with CRH, intracellular POMC-luciferase activity was significantly higher from the stimulation observed with transfection of the parental POMC-luciferase construct. In agreement with a previous report, CRH inhibited the constitutive NF-κB DNA-binding activity in AtT20 cells, as shown by electrophoretic mobility-shift assay, as soon as within 15 min of treatment. These effects of CRH were blocked by the CRH-R1 antagonist CP154,256. Our findings provide evidence that the regulation of corticotroph NF-κB activity by CRH is related to the activation of the pituitary POMC gene and, thus, may play an important role in stress response. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M313063200 |