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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2007-6-28
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pubmed:abstractText |
The dynamic interplay between serotonin [5-hydroxytryptamine (5-HT)] neurotransmission and the hypothalamic-pituitary-adrenal (HPA) axis has been extensively studied over the past 30 years, but the underlying mechanism of this interaction has not been defined. A possibility receiving little attention is that 5-HT regulates upstream corticotropin-releasing hormone (CRH) signaling systems via activation of serotonin 2C receptors (5-HT(2C)Rs) in the paraventricular nucleus of the hypothalamus (PVH). Through complementary approaches in wild-type rodents and 5-HT(2C)R-deficient mice, we determined that 5-HT(2C)Rs are necessary for 5-HT-induced HPA axis activation. We used laser-capture PVH microdissection followed by microarray analysis to compare the expression of 13 5-HTRs. Only 5-HT(2C)R and 5-HT(1D)R transcripts were consistently identified as present in the PVH, and of these, the 5-HT(2C)R was expressed at a substantially higher level. The abundant expression of 5-HT(2C)Rs in the PVH was confirmed with in situ hybridization histochemistry. Dual-neurohistochemical labeling revealed that approximately one-half of PVH CRH-containing neurons coexpressed 5-HT(2C)R mRNA. We observed that PVH CRH neurons consistently depolarized in the presence of a high-affinity 5-HT(2C)R agonist, an effect blocked by a 5-HT(2C)R antagonist. Supporting the importance of 5-HT(2C)Rs in CRH neuronal activity, genetic inactivation of 5-HT(2C)Rs produced a downregulation of CRH mRNA and blunted CRH and corticosterone release after 5-HT compound administration. These findings thus provide a mechanistic explanation for the longstanding observation of HPA axis stimulation in response to 5-HT and thereby give insight into the neural circuitry mediating the complex neuroendocrine responses to stress.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenal Cortex Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Corticotropin-Releasing Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT1D,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Serotonin, 5-HT2C,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin 5-HT2 Receptor Agonists
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:ColmersWilliam FWF,
pubmed-author:ElmquistJoel KJK,
pubmed-author:HeislerLora KLK,
pubmed-author:NonogakiKatsunoriK,
pubmed-author:O'RahillyStephenS,
pubmed-author:PronchukNinaN,
pubmed-author:RaberJacobJ,
pubmed-author:TecottLaurence HLH,
pubmed-author:TungLoraineL,
pubmed-author:YeoGiles S HGS,
pubmed-author:ZhouLigangL
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pubmed:issnType |
Electronic
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pubmed:day |
27
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6956-64
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17596444-Adrenal Cortex Hormones,
pubmed-meshheading:17596444-Animals,
pubmed-meshheading:17596444-Corticotropin-Releasing Hormone,
pubmed-meshheading:17596444-Down-Regulation,
pubmed-meshheading:17596444-Hypothalamo-Hypophyseal System,
pubmed-meshheading:17596444-Male,
pubmed-meshheading:17596444-Mice,
pubmed-meshheading:17596444-Mice, Inbred C57BL,
pubmed-meshheading:17596444-Mice, Knockout,
pubmed-meshheading:17596444-Neurosecretory Systems,
pubmed-meshheading:17596444-Paraventricular Hypothalamic Nucleus,
pubmed-meshheading:17596444-Pituitary-Adrenal System,
pubmed-meshheading:17596444-RNA, Messenger,
pubmed-meshheading:17596444-Rats,
pubmed-meshheading:17596444-Rats, Sprague-Dawley,
pubmed-meshheading:17596444-Receptor, Serotonin, 5-HT1D,
pubmed-meshheading:17596444-Receptor, Serotonin, 5-HT2C,
pubmed-meshheading:17596444-Serotonin,
pubmed-meshheading:17596444-Serotonin 5-HT2 Receptor Agonists,
pubmed-meshheading:17596444-Stress, Physiological
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pubmed:year |
2007
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pubmed:articleTitle |
Serotonin activates the hypothalamic-pituitary-adrenal axis via serotonin 2C receptor stimulation.
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pubmed:affiliation |
Department of Clinical Biochemistry, Addenbrooke's Hospital and the University of Cambridge, Cambridge CB2 2QR, United Kingdom. lkh30@medschl.cam.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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