1. Hormonal Regulation of Protein Turnover Effect of the Endocrine System

2. 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?

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 Ca 2+ activated initiate degradation of myofibrillar proteins (except actin, MHC) –caspases activated by ROS, Ca 2+ 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 Fedele et al., J Appl Physiol, 2000 Lourard et al., J Clin Invest, 1992

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, Ca 2+ )  proteolysis when cortisol : insulin is >4 Van Cauter et al. Am J Physiol, 1992

7. Effects of glucose ingestion on cortisol:insulin during prolonged exercise Cortisol:insulin during 2 hr of exercise (70% VO 2max ) 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 (triiodothyronine—T 3 ) (stimulates synthesis) –stimulates protein synthesis (and RMR) –release not affected by exercise –type I fibers affected more than type II  T 3 increases expression of type I MHC & SERCA –affects Vmax, relaxation time