RECOMBINANT INSULIN-LIKE GROWTH FACTOR-II INHIBITS THE GROWTH-STIMULATING EFFECT OF GROWTH-HORMONE ON THE LIVER OF SNELL-DWARF MICE

The actions and interactions of recombinant insulin-like growth factor -I and -II (IGF-I and IGF-II), alone or in combination with human GH o n body growth and the growth of several organs were studied in the Sne ll dwarf mouse. IGF-I and -II stimulate to a similar extent sulfate in corporation into cartilage, and both IGFs increase body length and wei ght. IGF-II as well as IGF-I have clear effects on the size of the sub mandibular salivary glands, kidneys, and spleen. IGF-II, however, did not influence the weight of the lung, in contrast with IGF-I. GH treat ment alone resulted in growth of the liver, whereas both IGFs were ina ctive. Surprisingly, IGF-II and, to a lesser extent, IGF-I inhibited G H-induced growth of the liver. Glycogen storage in the liver was decre ased by treatment with IGF-II alone or in combination with GH, as show n by histological examination. It was not affected by GH, IGF-I, or GH plus IGF-I. Also, the size of the centrilobular hepatocytes was decre ased by treatment with IGF-II and IGF-II plus GH; GH alone had a hyper trophic effect, whereas IGF-I or GH plus IGF-I had none. In contrast t o GH, IGFs did not increase polyploidy. Treatment with IGF-II increase d the level of IGFBP-3, as did IGF-I or GH treatment, as shown by West ern ligand blotting. The IGFs appeared to have a greater effect on the induction of 38.5-kilodalton IGFBP-3 than GH, suggesting a different role in the regulation of glycosylation. In conclusion, IGF-I and IGF- II as well as GH have a stimulatory effect on general body growth and are effective in the stimulation of serum IGFBP-3, sulfate incorporati on into cartilage, as well as the growth of specific organs in Snell d warf mice. Both IGFs, alone or in combination with GH, show distinct e ffects on the growth of the liver with respect to several histological parameters, which require further exploration.