THE INFLUENCE OF ENDOCRINE FACTORS ON THE SERUM CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-BINDING PROTEINS

Serum insulin-like growth factor-I (IGF-I) levels in lit (isolated GH deficiency), dw (panhypopituitarism), hyt (hypothyroidism) and cog (co ngenital goiter) mutant mice were found to be significantly lower than in control mice. In addition, liver and kidney IGF-I concentrations i n mutants were also found to be significantly reduced compared with co ntrols. These differences in IGF-I concentration were not observed in pg (genetic IGF receptor or post-receptor defect?) mice. These results indicated that serum IGF-I production is induced by thyroid hormones as well as by GH. Western blot analysis of serum IGF-binding protein ( IGFBP) fractions revealed the following differences among the five mut ants: the triplet of IGFBP-3 (42, 45 and 49 kDa) and IGFBP-4 (24 kDa) levels were significantly reduced. IGFBP-2 (32 kDa) levels were also r educed in the lit, hyt and cog mice, although the level in serum of dw mice was found to be greatly elevated. No differences in serum IGFBP levels were found in the pg mouse. Consequently, the ratio of IGFBP-3% :IGFBP-2% (the percentage of IGFBP-3 fraction of total IGFBP (IGFBP-3% ) divided by that of IGFBP-2 (IGFBP-2%)) was decreased in GH-deficient mice but increased ill hypothyroid mice, suggesting that IGFBP-3 and IGFBP-2 production in the liver is induced by GH and thyroid hormones respectively.