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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 both normals and dwarfs, serum IGF-II levels were highest soon after birth and dropped steadily thereafter. Western ligand blots of serum IGFBPs with 125I-IGF-II as tracer revealed the expected bands 41·5, 38·5, 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 treatment with growth hormone (GH) and/or thyroxine (T4) for 4 weeks. In spite of a comparable growth response obtained using these hormones, serum IGF-I was increased only by GH treatment; a small but significant decrease of serum IGF-II was obtained following GH or T4 treatment. An increase of the IGFBP-3 doublet was only obtained with GH; T4 and GH+T4 had no effect. The rise of IGFBP-3 after GH treatment was accompanied by the formation of the IGFBP 150 kDa complex, as measured by neutral gel chromatography. The size distribution of 125 I-IGF-II was restored to normal, while with 125I-IGF-I only a small peak at 150 kDa was observed. Elution profiles of sera after treatment with T4 or GH+T4 were identical to those of dwarf controls.
The presence of the IGFBPs was investigated in media conditioned by liver and lung explants of normal and dwarf animals. In culture media of liver explants from normal 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 predominated. 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 not be detected. We were unable to identify the 150 kDa IGFBP-complex in this medium using the size distribution of 125I-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 serum IGFBP-3 and IGF-I are regulated by GH and not by T4. In dwarf Snell mice, serum IGF-II is down regulated by GH as well as T4. The 150 kDa IGFBP complex is absent in dwarfs and, when induced by GH, seems to have a high affinity for IGF-II.
Journal of Endocrinology (1994) 143, 191–198
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