Corticotropin-releasing Factor 2 Receptor Localization in Skeletal Muscle

Samuelsson, Steven J.; Lange, Jana S.; Hinkle, Richard T.; Tarnopolsky, Mark A.; Isfort, Robert J.

doi:10.1369/jhc.4a6279.2004

Cited by 13 publications

(9 citation statements)

References 41 publications

(6 reference statements)

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“…This observation agrees with previous studies showing that administration of urocortin II (a CRF2R agonist) resulted in an increase in muscle mass in non‐atrophying muscles 17. Samuelsson et al33 showed that CRF2R in skeletal muscle was localized to neural structures, blood vessels, myotendinous junctions, and endomysial/perimysial spaces. Expression of CRF2R in skeletal muscle myocytes was not observed.…”

Section: Discussionsupporting

confidence: 91%

Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells

et al. 2007

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Previous studies have demonstrated an effect of corticotropin-releasing factor 2 receptor (CRF2R) agonists in the maintenance of skeletal muscle mass. The aim of this study was to evaluate the effects of a CRF2R agonist in preserving skeletal muscle in a mouse cachexia model. Implantation of a fast-growing tumor to mice (Lewis lung carcinoma) resulted in a clear cachectic state characterized by a profound muscle wasting. We found that administration of a CRF2R agonist (PG-873637) at 100 microg/kg/day by means of osmotic minipumps to tumor-bearing mice resulted in beneficial effects on muscle weight loss. Thus, muscle loss was partially reversed by the CRF2R agonist at different stages of tumor growth (at day 14 after tumor inoculation: 12% in tibialis posterior; 9% in gastrocnemius; and 48% in soleus). Moreover, the CRF2R agonist significantly reduced both the number of metastases and their mass (at day 19 after tumor inoculation: 66% and 61%, respectively). These data suggest a potentially beneficial effect of the CRF2R agonist in preserving skeletal muscle during cancer cachexia and open a line of research for the development of new therapeutic approaches for the treatment of muscle wasting associated with cancer.

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Section: Discussionsupporting

confidence: 91%

Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells

et al. 2007

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“…In the present study we demonstrated, using specific mCRFR2 RNase protection assays, RT-PCR, and DNA sequencing, that adult SM tissue expresses CRFR2␤, but not the CRFR1, transcripts. Previous reports showed CRFR2␤ expression in SM to be localized in neural structures, blood vessels, myotendinous junctions, and endomysial/ perimysial spaces, but not in myocytes (45).…”

Section: Discussionmentioning

confidence: 82%

Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2β in Developing and Mature Mouse Skeletal Muscle

Kuperman

Issler

Vaughan

et al. 2011

Molecular Endocrinology

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Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2 expression. Here, we demonstrate the exclusive expression of CRFR2, and not CRFR1, in mature SM tissue using RT-PCR and ribonuclease protection assays and report a differential expression of CRF receptors during C2C12 myogenic differentiation. Whereas C2C12 myoblasts exclusively express CRFR1, the C2C12 myotubes solely express CRFR2. Using cAMP luciferase assays and calcium mobilization measurements, we further demonstrate the functionality of these differentially expressed receptors. Using luciferase reporter assays we show a differential activation of CRFR promoters during myogenic differentiation. Transfections with different fragments of the 5'-flanking region of the mCRFR2β gene fused to a luciferase reporter gene show a promoter-dependent expression of the reporter gene and reveal the importance of the myocyte enhancer factor 2 consensus sequence located at the 3'-proximal region of CRFR2β promoter. Furthermore, we demonstrate that CRFR2 gene transcription in the mature mouse is stimulated by both high-fat diet and chronic variable stress conditions. Performing a whole-genome expression microarray analysis of SM tissues obtained from CRFR2-null mice or wild-type littermates revealed a robust reduction in retinol-binding protein 4 expression levels, an adipokine whose serum levels are elevated in insulin-resistant states. In correlation with the SM CRFR2β levels, the SM retinol-binding protein 4 levels were also elevated in mice subjected to high-fat diet and chronic variable stress conditions. The current findings further position the SM CRFR2 pathways as a relevant physiological system that may affect the known reciprocal relationship between psychological and physiological challenges and the metabolic syndrome.

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“…17 The CRF2R protein is localized in neuromuscular and myotendinous junctions as well as in endomysium and perimysium surrounding muscle fibers in rats, mice, and humans; however, expression was not observed in myocytes. 31 Blood vessels have also been shown to express the CRF2R protein. 31 Recently, it was shown that sauvagine, a nonselective CRFR agonist, completely inhibited muscle atrophy in casted CRF1R knockout mice.…”

mentioning

confidence: 99%

“…31 Blood vessels have also been shown to express the CRF2R protein. 31 Recently, it was shown that sauvagine, a nonselective CRFR agonist, completely inhibited muscle atrophy in casted CRF1R knockout mice. 17 However, the same treatment with noncasted mice had no significant effect on muscle mass.…”

mentioning

confidence: 99%

Effects of a CRF2R agonist and exercise on mdx and wildtype skeletal muscle

Hall¹,

Kaczor²,

Hettinga³

et al. 2007

Muscle and Nerve

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Corticotrophin-releasing factor 2 receptor (CRF2R) agonists prevent muscle atrophy due to immobilization, denervation, and corticosteroid-induced muscle atrophy in wildtype mice. We hypothesized that a CRF2R agonist will increase skeletal muscle mass in mdx mice. Mdx (C57BL/10ScSn-Dmd(mdx)) and wildtype (C57BL/6) mice were divided into four groups: sedentary placebo, sedentary CRF2R agonist, exercised placebo, and exercised CRF2R agonist. Mice exercised on a treadmill twice weekly for 30 min (8-12 m/min, 8 weeks). Muscle and heart weights, serum creatine kinase, and gamma-glutamyltransferase activities were measured. The CRF2R agonist increased extensor digitorum longus and soleus muscle weights (P < 0.05) in wildtype and mdx mice. Sedentary mdx CRF2R and exercised mdx placebo mice had lower serum creatine kinase activity than sedentary mdx placebo mice. CRF2R-treated mice had decreased heart weights compared to placebo-treated mice. We conclude that CRF2R agonists should be further evaluated as a potential therapy for dystrophinopathies.

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Corticotropin-releasing Factor 2 Receptor Localization in Skeletal Muscle

Cited by 13 publications

References 41 publications

Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells

Effects of CRF2R agonist on tumor growth and cachexia in mice implanted with Lewis lung carcinoma cells

Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2β in Developing and Mature Mouse Skeletal Muscle

Effects of a CRF2R agonist and exercise on mdx and wildtype skeletal muscle

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