Differential regulation of corticotropin-releasing hormone mRNA in rat brain

Corticotropin-releasing hormone (CRH), a major hypothalamic component of the hypothalamic-pituitary-adrenal axis, has been localized to both the paraventricular nucleus (PVN) and cerebral cortex. Adrenalectomy causes an increase in PVN CRH content, whereas its effect on cortical CRH content is not clear. In the present study, adrenalectomy resulted in a threefold rise in the CRH mRNA content of anatomic micropunches of the PVN of individual rats (P less than 0.001), which was abolished by dexamethasone replacement. In parietal cortex, adrenalectomy did not affect CRH mRNA content, whereas hypophysectomy resulted in a twofold rise in CRH mRNA content (P less than 0.02), which was not significantly reduced by dexamethasone replacement. These results demonstrate that the CRH gene is negatively regulated by glucocorticoid in the PVN but not in cerebral cortex and that the increase in cortical CRH mRNA content after hypophysectomy may be evidence for negative regulation of cortical CRH gene expression by a second pituitary-dependent factor other than glucocorticoid.