Transcript Hormonal Regulation of Protein Turnover

Hormonal Regulation of Protein
Turnover
Effect of the Endocrine System
Protein Turnover
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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 translation
Lourard et al., J
Clin Invest, 1992
Fedele et al., J
Appl Physiol, 2000
Hormonal Regulation of
Protein Turnover
 Cortisol (stimulates catabolism)
– released in response to stress
•  gluconeogenesis
– principal catabolic hormone
• stimulates ubiquitinproteosome 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 androgensensitive 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