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 > 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 • inhibitsubiquitin-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 >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% 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 (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