hormonal regulation of protein turnover effect of the endocrine system
TRANSCRIPT
Hormonal Regulation of Protein Turnover
Effect of the Endocrine System
Protein Turnover
synthesis is energy expensive turnover rate > than for CHO or TG synthesis energy cost is 2X that of glycogen or TG synthesis and breakdown are separately regulated
processes turnover rate varies (15 min – 3 wk) synthesis and breakdown affected by
four proteolytic processes in skeletal muscle gender, age, exercise, amino acid availability, dietary
carbohydrate, glucoregulatory hormones, intrinsic factors?
Proteolysis
ubiquitin-proteosome system – accounts for ~80% of total protein breakdown– proteins selected for degradation are conjugated (attached) to
ubiquitin then transported to large proteasomes other proteolytic systems
– lysosomes, – calpains
• Ca2+ activated• initiate degradation of myofibrillar proteins (except actin,
MHC)– caspases
• activated by ROS, Ca2+ • can cleave actomyosin and cytoskeleton proteins
Effect of exercise, amino acids, and glucose on protein turnover
Rasmussen & Phillips. Exerc Sport Sci Rev, 2003
Hormonal Regulation of Protein Turnover
Insulin (stimulates synthesis)
– released in response to elevated blood glucose
– suppresses protein degradation
– inhibits ubiquitin-proteosome, calpain, and caspase systems
– increases amino acid uptake– stimulates synthesis
transcription and translationFedele et al., J
Appl Physiol, 2000
Lourard et al., J Clin Invest, 1992
Hormonal Regulation of Protein Turnover
Cortisol (stimulates catabolism)
– released in response to stress gluconeogenesis
– principal catabolic hormone• stimulates ubiquitin-
proteosome system– requires co-factor (e.g.,
exercise, muscle damage, ROS, Ca2+)
proteolysis when cortisol : insulin is >4
Van Cauter et al. Am J Physiol, 1992
Effects of glucose ingestion on cortisol:insulin during prolonged exercise
Cortisol:insulin during 2 hr of exercise (70% VO2max) in postabsorptive state. Data demonstrates how strongly proteolysis is stimulated during prolonged exercise in postabsorptive state. (MacLaren et al., J Appl Physiol, 1999)
Hormonal Regulation of Protein Turnover
Growth hormone (stimulates synthesis mildly)
– released during exercise– by itself, not a major factor of protein synthesis
• greater effect on children/adolescents
Insulinlike Growth Factor I (IGF-1) (stimulates synthesis)
– has synergistic relationship with GH– stimulates protein synthesis and inhibits degradation
• inhibits proteolytic pathways
Hormonal Regulation of Protein Turnover
Androgens (stimulates synthesis)
– increases muscle synthesis w/ no effect on degradation
– binds to androgen receptor, which stimulates androgen-sensitive target genes
– testosterone administration increases androgen receptor numbers
• also increased by resistance exercise
Bhasin et al., N Engl J Med, 1996
Relation of [testosterone] and FFM
Bhasin et al. Am J Physiol, 2001
Hormonal Regulation of Protein Turnover
Thyroid hormone (triiodothyronine—T3) (stimulates
synthesis)
– stimulates protein synthesis (and RMR)– release not affected by exercise– type I fibers affected more than type II
T3 increases expression of type I MHC & SERCA
– affects Vmax, relaxation time