Absence of glucocorticoids augments stress-induced Mkp1 mRNA expression within the hypothalamic-pituitary-adrenal axis.
Absence of glucocorticoids augments stress-induced Mkp1 mRNA expression within the hypothalamic-pituitary-adrenal axis.
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DOI：
10.1530/joe-13-0365
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Spencer RL
中科院分区：
文献类型：
--
作者：
Osterlund CD;Thompson V;Hinds L;Spencer RL
Stress-induced activation of hypothalamic paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons triggers CRH release and synthesis. Recent findings suggest that this process depends on the intracellular activation (phosphorylation) of extracellular-regulated kinase 1 and 2 (ERK1/2) within CRH neurons. We have recently shown that the presence of glucocorticoids constrains stress-stimulated phosphorylation of PVN ERK1/2. In some peripheral cell types, dephosphorylation of ERK has been shown to be promoted by direct glucocorticoid upregulation of the MAP-kinase phosphatase-1 (Mkp-1) gene. In this study we tested the prospect that glucocorticoids regulate Mkp-1 mRNA expression in neural forebrain (medial-prefrontal cortex,mPFC, and PVN) and endocrine tissue (anterior pituitary) by subjecting young adult male Sprague-Dawley rats to various glucocorticoid manipulations ± acute psychological stress (restraint). Restraint led to a rapid increase in Mkp-1 mRNA within the mPFC, PVN and anterior pituitary, and this increase did not require glucocorticoid activity. In contrast to glucocorticoid upregulation of Mkp-1 gene expression in peripheral tissues, we found that the absence of glucocorticoids (via adrenalectomy) augmented basal mPFC and stress-induced PVN and anterior pituitary Mkp-1 gene expression. Taken together, this study indicates that the presence of glucocorticoids may constrain Mkp-1 gene expression in neural forebrain and endocrine tissues. This possible constraint may be an indirect consequence of the inhibitory influence of glucocorticoids on stress-induced activation of ERK1/2, a known upstream positive regulator of Mkp-1 gene transcription.
