IGF‐I and IGF‐II are growth‐stimulating peptides with strong mitogenic properties. These polypeptide growth factors circulate in serum bound to specific binding proteins. We report the cloning and complete sequence of a cDNA encoding a low mol. wt IGF‐binding protein from a human placenta cDNA library. We propose the designation IGF‐binding protein 1 (IBP‐1) for the gene and corresponding protein. Expression of the cDNA encoding IBP‐1 in COS cells resulted in the synthesis of a 30‐kd protein which binds IGF‐I and is immunologically indistinguishable from the IGF‐binding protein isolated from amniotic fluid or human serum. Northern blotting analysis demonstrated that expression of the IBP‐1 gene is highly tissue specific and limited to placental membranes and fetal liver suggesting a rigid control. The IBP‐1 gene is a single copy gene, located on chromosome 7. The results obtained suggest that most, if not all, lower mol. wt IGF‐binding proteins originate from this gene.

Expression of the insulin-like growth factor (IGF) system was investigated in mouse renal development and physiology, using non radioactive in situ hybridization and quantitative RT-PCR. IGF-I mRNA levels increased after birth and were confined to distal tubules and peritubular capillaries in the outer medulla. IGF-II mRNA levels were high in developing kidneys and peaked after birth. The type I receptor mRNA expression pattern mostly parallelled those of IGF-I and IGF-II. The IGF binding proteins (IGFBP's) showed weak mRNA expression for IGFBP-1 and -6. High fetal mRNA levels were measured for IGFBP-2, showing a similar profile in time as observed for IGF-II. Low fetal IGFBP-3 and -5 mRNA levels increased after birth. IGFBP-2, -4 and -5 mRNA expression was localized to differentiating cells. In the mature kidney predominant expression was confined to proximal tubules (IGFBP-4), thin limbs of Henle's Loop (IGFBP-2), glomerular mesangial cells (IGFBP-5) and peritubular capillaries of the medulla (IGFBP-5). IGFBP-3 mRNA was exclusively expressed in endothelial cells of the renal capillary system. Distinct mRNA expression for each member of the IGF system may point to specific roles in development and physiology of the mouse kidney.

The administration of a GHR antagonist in uninephrectomized adult mice has renal effects without affecting circulating levels of GH/IGFs, indicating that the effect of G120K-PEG may be mediated through a direct inhibitory effect on renal IGF-I accumulation through the renal GHR. This study shows, to our knowledge for the first time, that CRG in adult mice is strictly GH dependent.