INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING-PROTEINS AND THEIR MESSENGER-RNAS IN CONNECTIVE TISSUES OF FASTED GUINEA-PIGS

Lasting (with vitamin C-supplementation) and vitamin C-deficiency in g uinea-pigs are associated with decreased collagen gene expression in c onnective tissues. Recently we presented evidence that circulating ins ulin-like growth factor binding protein (IGFBP)-1 and -2 that are indu ced during both nutritional deficiencies may be responsible for this i nhibition by interfering with ICF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role fo r them. IGFBP-1 mRNA was not detected in any of the connective tissues . The protein, as measured by ligand blotting was not present in tissu es of normal animals but accumulated early during fasting in all of th e tissues. Bone and cartilage from normal animals contained IGFBP-2 an d its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fa sted guineapigs. Little or no IGFBP-3 was detected in normal tissue ex tracts, but protein accumulated during fasting and presumably was deri ved from the circulation. IGF-I and -II mRNAs were expressed in bone a nd cartilage but in skin, only IGF-II mRNA was detected. Affinity cros s-linking revealed that in skin, IGFBP-3 contained relatively few unoc cupied IGF-I binding sites compared to IGFBP-1 while in bone and carti lage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inh ibition of IGF-I-dependent collagen gene expression during fasting.