Impaired basal and restraint-induced epinephrine secretion in corticotropin-releasing hormone-deficient mice

CRH is thought to play a role in responses of the adrenocortical and adreno medullary systems during stress. To investigate the role of CRH in stress-i nduced secretions of corticosterone and epinephrine, we subjected wild-type (WT) and CRH-deficient (knockout, KO) mice to restraint, and analyzed plas ma corticosterone, plasma catecholamines, and adrenal phenylethanolamine N- methyltransferase (PNMT) gene expression and activity before and during 3 h of restraint. Plasma corticosterone increased over 40-fold in WT mice, but minimally in CRH KO mice. Adrenal corticosterone content tended to increas e in CRH KO mice, although to levels 5-fold lower than that in WT mice. CRH KO mice had significantly lower plasma epinephrine and higher norepinephri ne than WT mice at baseline, and delayed epinephrine secretion during restr aint. Adrenal PNMT messenger RNA content in CRH KO mice tended to be lower than that in WT mice, though the degree of induction was similar in both ge notypes. PNMT enzyme activity was significantly lower in CRH KO mice. Pharm acological adrenalectomy abolished restraint-induced corticosterone secreti on and PNMT gene expression in WT mice, consistent with an absolute require ment of glucocorticoids for PNMT gene expression. We conclude that glucocor ticoid insufficiency in CRH KO mice leads to decreased basal and restraint- induced plasma epinephrine and adrenal PNMT gene expression and enzyme acti vity.