Faculty Publications
Publication Date
2001
Disciplines
Endocrinology
Abstract
Two receptors (CRH receptor type 1 and CRH receptor type 2) have been identified for the stress-induced neuropeptide, CRH and related peptides, urocortin, and urocortin II. We previously found marked down-regulation of cardiac CRH receptor type 2 expression following administration of bacterial endotoxin, lipopolysaccharide, a model of systemic immune activation, and inflammation. We postulated that inflammatory cytokines may regulate CRH receptor type 2. We show that systemic IL-1α administration significantly down-regulates CRH receptor type 2 mRNA in mouse heart. In addition, TNFα treatment also reduces CRH receptor type 2 mRNA expression, although the effect was not as marked as with IL-1α. However, CRH receptor type 2 mRNA expression is not altered in adult mouse ventricular cardiomyocytes stimulated in vitro with TNFα or IL-1α. Thus, cytokine regulation may be indirect. Exogenous administration of corticosterone in vivo or acute restraint stress also reduces cardiac CRH receptor type 2 mRNA expression, but like cytokines, in vitro corticosterone treatment does not modulate expression in cardiomyocytes. Interestingly, treatment with urocortin significantly decreases CRH receptor type 2 mRNA in cultured cardiomyocytes. We speculate that in vivo, inflammatory mediators such as lipopolysaccharide and/or cytokines may increase urocortin, which in turn down-regulates CRH receptor type 2 expression in the heart. Because CRH and urocortin increase cardiac contractility and coronary blood flow, impaired CRH receptor type 2 function during systemic inflammation may ultimately diminish the adaptive cardiac response to adverse conditions.
Document Type
Published Version
Original Citation
Sarah C. Coste, Kurt A. Heldwein, Susan L. Stevens, Eric Tobar-Dupres, Mary P. Stenzel-Poore
IL-1α and TNF-α down-regulate CRH receptor-2 mRNA expression in the mouse heart.
Endocrinology, 2001, volume 142, issue 8, pages 3537-3545
doi: 10.1210/endo.142.8.8342
DigitalCommons@Linfield Citation
Coste, Sarah C.; Heldwein, Kurt A.; Stevens, Susan L.; Tobar-Dupres, Eric; and Stenzel-Poore, Mary P., "IL-1α and TNF-α Down-Regulate CRH Receptor-2 mRNA Expression in the Mouse Heart" (2001). Faculty Publications. Published Version. Submission 7.
https://digitalcommons.linfield.edu/hhpafac_pubs/7
Comments
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