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, vitamins, 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 IGF-I would be enhanced IGFBP-3 protease activity. By day 30, caloric deprivation to 40% lowered serum GH, GHBP, IGF-I and IGFBP-3, and liver IGF-I mRNA. This was the only condition resulting in body weight loss (-15%) vs 39% gain in controls. Restriction to 60% calories had no impact on BP levels, slightly lowered IGF-I (-12%) in the face of a 95% inhibition of GH levels, 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 conditions could not be explained by an increase in IGFBP-3 protease activity, or a decrease in the association of IGF-I with IGFBP-3 and the acid labile subunit.
Oster
M H
MH
Endocrine Research Department, Genentech, Inc., South San Francisco, California 94080, USA.
Fielder
P J
PJ
Levin
N
N
Cronin
M J
MJ
D000591:Amino Acid Isomerases / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000097:blood; D018833:Chaperonins / Q000096:biosynthesis; D018753:Diet, Protein-Restricted; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D013006:Growth Hormone / Q000096:biosynthesis* / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D019696:Peptidylprolyl Isomerase; D010865:Pilot Projects; D011502:Protein-Energy Malnutrition / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D018833:Chaperonins; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; C051815:somatotropin-binding protein