Hormonal Regulation of Protein Turnover

1
Hormonal Regulation of Protein Turnover

• Effect of the Endocrine System

2
Protein Turnover

• synthesis is energy expensive
• turnover rate gt 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?

3
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

4
Effect of exercise, amino acids, and glucose on
protein turnover
Rasmussen Phillips. Exerc Sport Sci Rev, 2003
5
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
6
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 gt4

Van Cauter et al. Am J Physiol, 1992
7
Effects of glucose ingestion on cortisolinsulin
during prolonged exercise
Cortisolinsulin 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)
8
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

9
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
10
Relation of testosterone and FFM
Bhasin et al. Am J Physiol, 2001
11
Hormonal Regulation of Protein Turnover

• Thyroid hormone (triiodothyronineT3) (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