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 adrenomedullary systems during stress. To investigate the role of CRH in stress-induced secretions of corticosterone and epinephrine, we subjected wild-type (WT) and CRH-deficient (knockout, KO) mice to restraint, and analyzed plasma 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 increase 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 norepinephrine than WT mice at baseline, and delayed epinephrine secretion during restraint. 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 genotypes. PNMT enzyme activity was significantly lower in CRH KO mice. Pharmacological adrenalectomy abolished restraint-induced corticosterone secretion and PNMT gene expression in WT mice, consistent with an absolute requirement of glucocorticoids for PNMT gene expression. We conclude that glucocorticoid insufficiency in CRH KO mice leads to decreased basal and restraint-induced plasma epinephrine and adrenal PNMT gene expression and enzyme activity.
Jeong
K H
KH
Division of Endocrinology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jacobson
L
L
Pacák
K
K
Widmaier
E P
EP
Goldstein
D S
DS
Majzoub
J A
JA
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics; D004837:Epinephrine / Q000378:metabolism*; D005938:Glucocorticoids / Q000097:blood; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
D005938:Glucocorticoids; D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone; D014446:Tyrosine 3-Monooxygenase; D003345:Corticosterone; D004837:Epinephrine