ALTERED GROWTH OF MICE DIVERGENTLY SELECTED FOR BODY-WEIGHT IS ASSOCIATED WITH COMPLEX CHANGES IN THE GROWTH HORMONE INSULIN-LIKE GROWTH-FACTOR SYSTEM/

Mice investigated in this study were generated by selecting a sub-popu lation of the NMRI out-bred stock (C), for high (H) or low (L) 8-week body weight. After 58 generations of selection, 8-week body weights of the sub-populations were markedly different if compared to controls. To investigate endocrine changes causing the altered growth performanc e in the different lines of mice, we analysed several components of th e growth hormone (GH)/insulin-like growth factor (IGF) system. Pituita ry weights of male and female L mice were significantly smaller than t hose of C and H mice. Relative to body weight, pituitary weights of ma le mice from the three lines did not differ, however pituitary weight- to-body weight-ratios of female L mice were significantly greater than those of H females. Mean volume densities of somatotropic cells were significantly smaller in L mice than in C and H mice. Serum IGF-I conc entrations were significantly lower in the L line than in the C and H lines. H mice displayed significantly increased serum insulin levels b oth after ad libitum feeding and after a 14 hour fasting period. Ligan d blot analysis of serum IGF-binding proteins (IGFBPs) revealed a sign ificant reduction of circulating IGFBP-3 in L mice as compared to C an d H mice. In contrast, serum IGFBP-2 mRNA levels were significantly in creased in male L mice and showed non significant increases in female L mice. Hepatic IGFBP-2 mRNA levels were significantly increased in L mice and decreased in H mice as compared to C mice. Expression of IGFB P-4 mRNA in the liver was significantly decreased in both selection li nes (L, H) as compared to the random-bred controls. Our findings demon strate that altered growth of mice resulting from selection for body w eight is associated with complex changes in the endocrine network of t he GH/IGF system. (C) 1998 Churchill Livingstone