Document Detail

The thyrotropin-releasing hormone (TRH)-immune system homeostatic hypothesis.
MedLine Citation:
PMID:  19000920     Owner:  NLM     Status:  MEDLINE    
Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormone (TRH) hypothesis of homeostatic regulation: implications for TRH-based therapeutics. J Pharmacol Exp Ther 305(2):410-416.] and Yarbrough et al. [Yarbrough, G.G., Kamath, J., Winokur, A., Prange, A.J. Jr. (2007). Thyrotropin-releasing hormone (TRH) in the neuroaxis: therapeutic effects reflect physiological functions and molecular actions. Med Hypotheses 69(6):1249-1256.] provided a functional framework, predicated on its global homeostatic influences, to conceptualize the numerous interactions of TRH with the central nervous system (CNS) and endocrine system. Herein, we profer a similar analysis to interactions of TRH with the immune system. Autocrine/paracrine cellular signaling motifs of TRH and TRH receptors are expressed in several tissues and organs of the immune system. Consistent with this functional distribution, in vitro and in vivo evidence suggests a critical role for TRH during the developmental stages of the immune system as well as its numerous interactions with the fully developed immune system. Considerable evidence supports a pivotal role for TRH in the pathophysiology of the inflammatory process with specific relevance to the "cytokine-induced sickness behavior" paradigm. These findings, combined with a number of documented clinical actions of TRH strongly support a potential utility of TRH-based therapeutics in select inflammatory disorders. Similar to its global role in behavioral and energy homeostasis a homeostatic role for TRH in its interactions with the immune system is consonant with the large body of available data. Recent advances in the field of immunology provide a significant opportunity for investigation of the TRH-immune system homeostatic hypothesis. Moreover, this hypothesis may provide a foundation for the development of TRH-based therapeutics for certain medical and psychiatric disorders involving immune dysfunction.
J Kamath; G G Yarbrough; A J Prange; A Winokur
Publication Detail:
Type:  Journal Article; Review     Date:  2008-10-21
Journal Detail:
Title:  Pharmacology & therapeutics     Volume:  121     ISSN:  0163-7258     ISO Abbreviation:  Pharmacol. Ther.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-26     Completed Date:  2009-03-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905840     Medline TA:  Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  20-8     Citation Subset:  IM    
University of Connecticut Health Center, Department of Psychiatry, 263 Farmington Avenue, Farmington, CT 06030, United States.
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MeSH Terms
Central Nervous System / metabolism
Drug Discovery
Immune System Processes / drug effects,  physiology*
Inflammation* / drug therapy
Models, Immunological*
Neuroimmunomodulation / physiology
Receptors, Thyrotropin-Releasing Hormone / metabolism
Thyrotropin-Releasing Hormone / metabolism,  pharmacology,  physiology*
Reg. No./Substance:
0/Receptors, Thyrotropin-Releasing Hormone; 24305-27-9/Thyrotropin-Releasing Hormone

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