Role played by hypothalamic nuclear factor-{kappa}B in alcohol-mediated activation of the rat hypothalamic-pituitary-adrenal axis.

Abstract:

:The DNA binding protein nuclear factor-kappaB (NF-kappaB) is a transcription factor translocated from the cytosol to the nucleus in response to stressors. Here we determined whether the known ability of alcohol to activate the hypothalamic-pituitary axis was mediated by NF-kappaB, tested the hypothesis that this phenomenon was accompanied by increased hypothalamic NF-kappaB transcripts, and investigated some of the mechanisms involved in this response. We found that alcohol-induced increase in plasma ACTH was blunted by the intracerebroventricular (icv) injection of a cell-permeable peptide that inhibits NF-kappaB translocation. Alcohol also increased hypothalamic inhibitory factor kappaB (IkappaB) mRNA levels, a factor that regulates NF-kappaB protein activation and the activity of NF-kappaB DNA binding and whose expression is thought to reflect NF-kappaB activity. This response, which was not accompanied by detectable changes in brain levels of proinflammatory cytokines, was partially retained in adrenalectomized/corticosterone-replaced rats. The icv injection of corticotropin-releasing factor (CRF), a hypothalamic peptide that is released by alcohol and mediates its influence on ACTH secretion, also stimulated hypothalamic IkappaB transcription. We therefore determined whether brain CRF played a role in the influence of alcohol on NF-kappaB signaling pathways. Indeed, the icv injection of the CRF antagonist alpha-helCRF(9-41) decreased alcohol-induced hypothalamic IkappaB transcripts. Because this antagonist did not alter corticosterone levels, our data suggest that the role played by CRF was not modulated by this steroid. Collectively, our results provide evidence for a functional interaction between alcohol and NF-kappaB-dependent pathway in stimulating the rat hypothalamic-pituitary axis activity that involves independent roles of corticosterone and CRF.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Lee S,Rivier C

doi

10.1210/en.2004-1268

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

2006-14

issue

4

eissn

0013-7227

issn

1945-7170

pii

en.2004-1268

journal_volume

146

pub_type

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