Urocortin II treatment reduces skeletal muscle mass and function loss during atrophy and increases nonatrophying skeletal muscle mass and function.
Two corticotropin-releasing factor 2 receptor (CRF2R)-selective peptides have been recently described, urocortin II (also known as stresscopin-related peptide) and urocortin III (stresscopin). We have used urocortin II to evaluate the effects of activation of the CRF2R on skeletal muscle-related physiological processes. Administration of urocortin II to mice prevented the loss of skeletal muscle mass resulting from disuse due to casting, corticosteroid treatment, and nerve damage. In addition, urocortin II treatment prevented the loss of skeletal muscle force and myocyte cross-sectional area that accompanied muscle mass losses resulting from disuse due to casting. Finally, we observed increased skeletal muscle mass and force in normal muscles when mice are treated with urocortin II. These results were confirmed using two additional CRF2R agonists, urocortin I and sauvagine. Thus, activation of the CRF2R modulates skeletal muscle mass in both normal and atrophying muscle. Therefore, CRF2R-selective agonists may find utility in the treatment of skeletal muscle wasting diseases including age-related muscle loss or sarcopenia.
Hinkle
Richard T
RT
Research Division, Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, Ohio 45040-9317, USA.
Donnelly
Elizabeth
E
Cody
David B
DB
Bauer
Mary Beth
MB
Isfort
Robert J
RJ
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000818:Animals; D016466:CHO Cells; D002370:Casts, Surgical / Q000009:adverse effects; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006224:Cricetinae; D006984:Hypertrophy; D008024:Ligands; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries; D054832:Urocortins; D014947:Wounds and Injuries / Q000150:complications
D000305:Adrenal Cortex Hormones; C101531:CRF receptor type 2; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C518358:urocortin 2, mouse; D003346:Corticotropin-Releasing Hormone