ADAPTATION OF THE GROWTH-HORMONE AND INSULIN-LIKE GROWTH-FACTOR-I AXIS TO CHRONIC AND SEVERE CALORIE OR PROTEIN-MALNUTRITION

The hierarchy of diet components (e,g,, protein, carbohydrate, vitamin s, and minerals) influencing growth hormone (GH), insulin-like growth factor-I (IGF-I), and their binding proteins (BP) is not well defined. Young adult rats were fed diets for 1 mo that included low protein or 60% and 40% of carbohydrate calories. We hypothesized that levels of both hormones, their dominant BPs and Liver IGF-I mRNA would fall, and that part of the mechanism for decreasing serum IGP-I would be enhanc ed IGFBP-3 protease activity. By day 30, caloric deprivation to 40% lo wered serum GH, GHBP, IGF-I and IGFBP-3, and liver IGF-I mRNA, This wa s the only condition resulting in body weight loss (-15%) vs 39% gain in controls. Restriction to 60% calories had no impact on BP levels, s lightly lowered IGF-I (-12%) in the face of a 95% inhibition of GH lev els, while allowing a modest 9% body weight gain. Protein deprivation lowered serum GH, IGF-I and IGFBP-3, and liver IGF-I mRNA, while GHBP levels were normal. The reduced total IGF-I under these dietary condit ions could not be explained by an increase in IGFBP-3 protease activit y, or a decrease in the association of IGF-I with IGFBP-3 and the acid labile subunit.