Dexamethasone decreases serum and liver IGF-I and maintains liver IGF-I mRNA in parenterally fed rats.
Insulin-like growth factor-I (IGF-I) gene expression is regulated by nutritional and hormonal factors. High-dose glucocorticoids decrease food intake, and this confounds studies addressing glucocorticoid effects on IGF-I gene regulation. We investigated alterations in the hepatic IGF-I endocrine system induced by a catabolic dose of dexamethasone (Dex) in rats given adequate nutrition by continuous infusion of total parenteral nutrition (TPN) solution with or without IGF-I administration. The four TPN groups included control, +Dex, +IGF-I, and +IGF-I + Dex (n = 9-11/group). Dex induced a 12% loss of body weight in association with a 50% decrease in hepatic immunoreactive IGF-I, a 10% decrease in serum IGF-I, and no change in steady-state liver IGF-I mRNA or growth hormone (GH) receptor binding. Exogenous IGF-I increased serum IGF-I, attenuated Dex-induced catabolism, and did not reduce hepatic levels of IGF-I and IGF-I mRNA despite decreased serum GH. These data suggest that Dex-induced catabolism is associated with downregulation of the hepatic IGF-I endocrine system at the translational or posttranslational level when adequate nutrition is provided.
Kritsch
K R
KR
Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Murali
S
S
Adamo
M L
ML
Ney
D M
DM
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000906:Antibodies; D003907:Dexamethasone / Q000494:pharmacology*; D004703:Endocrine System / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010289:Parenteral Nutrition, Total; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics
D000906:Antibodies; D005938:Glucocorticoids; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone