Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs

Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and-2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with IGF-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 for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting, was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guinea-pigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and-II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting.