INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II AND THEIR BINDING-PROTEINSDURING POSTNATAL-DEVELOPMENT OF DWARF SNELL MICE BEFORE AND DURING GROWTH-HORMONE AND THYROXINE THERAPY

The ontogeny of serum insulin-like growth factors (IGFs)-I and -II and their binding proteins (IGFBPs) was studied in normal and dwarf Snell mice. IGF-I concentrations in serum of normal mice increased between 4 and 8 weeks of age; dwarf mice had very low serum IGF-I levels. In b oth normals and dwarfs, serum IGF-II levels were highest soon after bi rth and dropped steadily thereafter. Western Ligand blots of serum IGF BPs with I-125-IGF-II as tracer revealed the expected bands of 41.5, 3 8.5, 30-32 and 24 kDa. In normal mice the IGFBP-3 doublet was already detectable at 2 weeks of age, and its intensity increased with age. In dwarf mice the IGFBP-3 doublet was hardly detectable. The changes of IGFs and their IGFBPs were studied in sera of dwarf mice after treatme nt with growth hormone (GH) and/or thyroxine (T-4) for 4 weeks. In spi te of a comparable growth response obtained using these hormones, seru m IGF-I was increased only by GH treatment; a small but significant de crease of serum IGF-II was obtained following GH or T-4 treatment. An increase of the IGFBP-3 doubler was only obtained with GH; T-4 and GHT-4 had no effect. The rise of IGFBP-3 after GH treatment was accompan ied by the formation of the IGFBP 150 kDa complex, as measured by neut ral gel chromatography. The size distribution of I-125-IGF-II was rest ored to normal, while with I-125-IGF-I Only a small peak at 150 kDa wa s observed. Elution profiles of sera after treatment with T-4 or GH+T- 4 were identical to those of dwarf controls. The presence of the IGFBP s was investigated in media conditioned by liver and lung explants of normal and dwarf animals. In culture media of Liver explants from norm al mice, bands at 30-32 and 24 kDa predominated; the intensity of the IGFBP-3 doublet was relatively low. In dwarfs the 30-32 kDa predominat ed. In culture media of the lung from normal mice the IGFBP-3 doublet and the 24 kDa band were clearly visible; in dwarf mice IGFBPs could n ot be detected. We were unable to identify the 150 kDa IGFBP-complex i n this medium using the size distribution of I-125-IGFs On neutral gel chromatography after incubation with the conditioned media. This was in contrast to data obtained with normal serum.Our data suggest that s erum IGFBP-3 and IGF-I are regulated by GH and not by T-4. In dwarf Sn ell mice, serum IGF-II is down regulated by GH as well as T-4. The 150 kDa IGFBP complex is absent in dwarfs and, when induced by GH, seems to have a high affinity for IGF-II.