Regulation of pituitary corticotropin releasing hormone receptors

Corticotropin releasing hormone (CRH) stimulates pituitary ACTH secretion t hrough type-1 CRH (CRH1) receptors. Stimulation of the hypothalamic pituita ry adrenal (HPA) axis as well as increased corticotroph responsiveness duri ng stress and adrenalectomy are associated with marked pituitary CRH bindin g downregulation. The presence of CRH1 receptors in the pituitary are essen tial to maintain ACTH secretion. Downregulation of CRH binding is associate d with normal or elevated levels of CRH1 receptor mRNA and this may contrib ute to the maintainence of permissive levels of CRH I receptors in the pitu itary. Injection of either CRH or glucocorticoids in rats in vivo induces C RH binding and CRH1 receptor mRNA downregulation, whereas their simultaneou s administration causes only transient CRH1 receptor mRNA loss. Vasopressin increases CRH1 receptor mRNA levels. This suggest that interactions betwee n CRH, vasopressin and glucocorticoids accounts for CRH1 receptor mRNA upre gulation during stress. The lack of correlation between CRH binding and CRH 1 receptor mRNA indicates that the major sites for pituitary CRH1 receptor regulation are at the post-transcriptional level. (C) 2001 Elsevier Science Inc. All rights reserved.