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