Absence of glucocorticoids augments stress-induced Mkp1 mRNA expression within the hypothalamic–pituitary–adrenal axis

Abstract

Stress-induced activation of hypothalamic paraventricular nucleus (PVN) corticotropin-releasing hormone (CRH) neurons trigger CRH release and synthesis. Recent findings have suggested that this process depends on the intracellular activation (phosphorylation) of 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 (Mkp1) gene. In this study, we tested the hypothesis that glucocorticoids regulateMkp1mRNA expression in the 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 with or without acute psychological stress (restraint). Restraint led to a rapid increase inMkp1mRNA within the mPFC, PVN, and anterior pituitary, and this increase did not require glucocorticoid activity. In contrast to glucocorticoid upregulation ofMkp1gene expression in the peripheral tissues, we found that the absence of glucocorticoids (as a result of adrenalectomy) augmented basal mPFC and stress-induced PVN and anterior pituitaryMkp1gene expression. Taken together, this study indicates that the presence of glucocorticoids may constrainMkp1gene expression in the 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 ofMkp1gene transcription.