title: Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue.
abstract: Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression.
authors.affiliation: Cell & Molecular Physiology (H166 Penn State College of Medicine, Hershey, PA 17033-0850, USA. clang@psu.edu
authors.forename: Qianning
authors.initials: Q
authors.lastname: Jiao
authors.forename: Anne M
authors.initials: AM
authors.lastname: Pruznak
authors.forename: Danuta
authors.initials: D
authors.lastname: Huber
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Vary
authors.forename: Charles H
authors.initials: CH
authors.lastname: Lang
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D015153:Blotting, Western; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002245:Carbon Dioxide / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D018149:Glucose Intolerance / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006728:Hormones / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009133:Muscular Atrophy / Q000473:pathology; D023282:Nuclease Protection Assays; D009919:Orchiectomy; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D006728:Hormones; D009124:Muscle Proteins; D002245:Carbon Dioxide; D007334:Insulin-Like Growth Factor I; D046988:Proteasome Endopeptidase Complex; D007930:Leucine