title: The modulator effect of GH on skeletal muscle lysosomal enzymes is dietary protein dependent.
abstract: OBJECTIVE
  The purpose of this work is to determine whether changes in dietary protein level could alter the modulator effect that GH has on the muscle lysosomal system by influencing the hydrolytic activities of cathepsin D, acid RNase and DNase II and the participation of these enzymes in muscle growth.
  
  
  METHODS
  BALB/c female mice were fed a diet containing 20% (HP) or 12% (MP) protein ad libitum and were treated with either saline (s) or rhGH (GH) (74 ng/g) for 29 days. Body weight and feed intake were recorded daily. At 25, 30, 35, 40, 45 and 50 days of age, five mice from each group were slaughtered and nucleic acids and protein concentrations and cathepsin D, acid RNase and DNase II activities in gastrocnemius muscle were analysed. Correlation coefficients were used to analyse the links between the activity of each enzyme with its substrate.
  
  
  RESULTS
  GH-treatment induced a depletion-recovery response in muscle growth through a compensatory mechanism. Changes in protein content, DNA and RNA concentrations were related to changes in lysosomal enzyme activities. Muscle cathepsin D activity in saline mice fell as the dietary protein concentration increased. GH-treatment reversed this effect by enhancing the proteolytic activity in muscle of well-fed mice and inhibiting it in mice fed a 12% protein diet. This inversion appears to be related to the different mechanism elicited by GH-treatment on skeletal muscle protein growth in each dietary group. An opposite trend was observed in muscle acid nuclease activities. Acid RNase and DNase II increased according to the dietary protein concentration, since a 12% protein diet induced a lower catabolism, especially on muscle DNA of saline mice. In contrast, GH-treatment decreased acid RNase and DNase II activities, but only in mice fed a 20% protein diet, perhaps leading to spare muscle RNA for protein synthesis, as well as to the inhibition of DNA degradation during catch-up growth. A lower dietary protein concentration appeared to reverse the GH protective effect on nucleic acids.
  
  
  CONCLUSIONS
  GH seems to act as a dietary protein-dependent modulator of the skeletal muscle lysosomal enzyme activity. These lysosomal enzymes play a role during muscle growth in GH-treated post-weaning mice by modifying muscle protein and DNA and RNA degradation.
authors.affiliation: Sección Departamental de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. elopez@farm.ucm.es
authors.forename: M E
authors.initials: ME
authors.lastname: López-Oliva
authors.forename: A
authors.initials: A
authors.lastname: Agis-Torres
authors.forename: E
authors.initials: E
authors.lastname: Muñoz-Martínez
mesh_terms: D000818:Animals; D002402:Cathepsin D / Q000032:analysis / Q000037:antagonists & inhibitors; D004247:DNA / Q000032:analysis; D004044:Dietary Proteins / Q000008:administration & dosage*; D004706:Endodeoxyribonucleases / Q000032:analysis / Q000037:antagonists & inhibitors; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D012313:RNA / Q000032:analysis; D012260:Ribonucleases / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D004044:Dietary Proteins; D009124:Muscle Proteins; D012313:RNA; D013006:Growth Hormone; D004247:DNA; D004706:Endodeoxyribonucleases; D012260:Ribonucleases; C019329:deoxyribonuclease II; D002402:Cathepsin D