Document Detail

Stress hormone synthesis in mouse hypothalamus and adrenal gland triggered by restraint is dependent on pituitary adenylate cyclase-activating polypeptide signaling.
MedLine Citation:
PMID:  19931358     Owner:  NLM     Status:  MEDLINE    
Stress responses are elicited by a variety of stimuli and are aimed at counteracting direct or perceived threats to the well-being of an organism. In the mammalian central and peripheral nervous systems, specific cell groups constitute signaling circuits that indicate the presence of a stressor and elaborate an adequate response. Pituitary adenylate cyclase-activating polypeptide (PACAP) is expressed in central and peripheral parts of these circuits and has recently been identified as a candidate for regulation of the stress axis. In the present experiments, we tested the involvement of PACAP in the response to a psychological stressor in vivo. We used a restraint paradigm and compared PACAP-deficient mice (PACAP-/-) to wild-type controls (PACAP+/+). Acute secretion of corticosterone elicited by 1 h of restraint was found to be identical between genotypes, whereas sustained secretion provoked by 6 h of unrelieved restraint was 48% lower in PACAP-/-mice. Within the latter time frame, expression of messenger RNA (mRNA) encoding corticotropin-releasing hormone (CRH) was increased in the hypothalamus of wild type, but not PACAP-deficient mice. Expression of the activity-regulated transcription factors Egr1 (early growth response 1) and Fos (FBJ osteosarcoma oncogene) in the hypothalamus was rapidly and transiently induced by restraint in a PACAP-dependent fashion, a pattern that was also found in the adrenal glands. Here, abundance of transcripts encoding enzymes required for adrenomedullary catecholamine biosynthesis, namely TH (tyrosine hydroxylase) and PNMT (phenylethanolamine N-methyltransferase), was higher in PACAP+/+ mice after 6 h of unrelieved restraint. Our results suggest that sustained corticosterone secretion, synthesis of the hypophysiotropic hormone CRH in the hypothalamus, and synthesis of the enzymes producing the hormone adrenaline in the adrenal medulla, are controlled by PACAP signaling in the mouse. These findings identify PACAP as a major contributor to the stimulus-secretion-synthesis coupling that supports stress responses in vivo.
N Stroth; L E Eiden
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2009-11-18
Journal Detail:
Title:  Neuroscience     Volume:  165     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-12     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1025-30     Citation Subset:  IM    
Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, MD 20892, USA.
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MeSH Terms
Adrenal Glands / enzymology,  metabolism*
Corticosterone / blood,  metabolism
Corticotropin-Releasing Hormone / metabolism
Early Growth Response Protein 1 / metabolism
Hormones / blood,  metabolism*
Hypothalamus / metabolism*
Mice, Inbred C57BL
Mice, Knockout
Phenylethanolamine N-Methyltransferase / metabolism
Pituitary Adenylate Cyclase-Activating Polypeptide / genetics,  metabolism*
Proto-Oncogene Proteins c-fos / metabolism
RNA, Messenger / metabolism
Restraint, Physical
Signal Transduction
Stress, Psychological / metabolism*
Time Factors
Tyrosine 3-Monooxygenase / metabolism
Grant Support
Z01 MH002386-23/MH/NIMH NIH HHS; ZIA MH002386-23/MH/NIMH NIH HHS
Reg. No./Substance:
0/Early Growth Response Protein 1; 0/Egr1 protein, mouse; 0/Hormones; 0/Pituitary Adenylate Cyclase-Activating Polypeptide; 0/Proto-Oncogene Proteins c-fos; 0/RNA, Messenger; 50-22-6/Corticosterone; 9015-71-8/Corticotropin-Releasing Hormone; EC 3-Monooxygenase; EC N-Methyltransferase

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