Modifying muscle mass - the endocrine perspective.
This review describes the major hormonal factors that determine the balance between human skeletal muscle anabolism and catabolism in health and disease, with specific reference to age-related muscle loss (sarcopenia). The molecular mechanisms associated with muscle hypertrophy are described, and the central role of the satellite cell highlighted. The biological dynamics of satellite cells, varying between states of quiescence, proliferation and differentiation are strongly influenced by local endocrine factors. The molecular mechanisms of muscle atrophy are examined focussing on the causes of sarcopenia and associations with systemic medical disorders. In addition, evidence is provided that the mechanisms of atrophy and hypertrophy are unlikely to be simple opposites. Novel endocrine mechanisms underpinning mechano-transduction include IGF-I subtypes that may differentiate between endocrine and mechanical signals; their interaction with classical endocrine factors is an active area of translational research. Recently acquired knowledge on the mechanism of anabolic effects of androgens is also reviewed. The increasingly recognised role of myostatin, a negative regulator of muscle function, is described, as well as its potential as a therapeutic target. Strategies to counter age-related sarcopenia thus represent an exciting field of future investigation.
Solomon
A M
AM
Department of Endocrinology, Royal Free Hospital and Medical School, Pond Street, London NW3 2PF, UK. a.solomon@medsch.ucl.ac.uk
Bouloux
P M G
PM
D000222:Adaptation, Physiological; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000728:Androgens / Q000502:physiology; D002986:Clinical Trials as Topic; D005260:Female; D006728:Hormones / Q000172:deficiency / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D055435:Myostatin; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism
D000728:Androgens; D006728:Hormones; C525911:MSTN protein, human; D055435:Myostatin; D016212:Transforming Growth Factor beta