Stimulation of intestinal growth is associated with increased insulin-like growth factor-binding protein 5 mRNA in the jejunal mucosa of insulin-like growth factor-I-treated parenterally fed rats.
Surgically stressed rats maintained with total parenteral nutrition (TPN) exhibit jejunal atrophy, which can be attenuated by insulin-like growth factor-I (IGF-I) but not by growth hormone (GH) treatment. In order to understand the basis for the selective action of IGF-I, the levels of mRNAs encoding IGF-I, IGF-binding proteins (IGFBPs), IGF-I receptor, and GH receptor/binding protein (GHR/GHBP) were determined in rats given TPN and treated with GH, IGF-I, or GH + IGF-I. GH treatment significantly stimulated hepatic IGF-I mRNA. IGF-I treatment did not alter liver IGF-I mRNA, nor was there any evidence for interaction between GH and IGF-I. Jejunal mucosa IGF-I mRNA was extremely low and was not altered by TPN or by any of the hormonal treatments. The inability of GH to stimulate jejunal growth was not associated with a deficiency in GHR/GHBP mRNA. In jejunal mucosa, IGF-I and GH treatment independently and synergistically stimulated IGFBP-3 mRNA. IGF-I stimulated jejunal IGFBP-5 mRNA, but GH had no effect on IGFBP-5 mRNA. The levels of IGF-I receptor and IGFBP-1, 2, 4, and 6 mRNAs were extremely low and/or were not altered by any of the treatments. These results suggest that the ability of exogenous IGF-I, but not GH, to induce IGFBP-5 mRNA in jejunal mucosa may lead to the selective growth-promoting effect of IGF-I. Jejunal mucosa IGFBP-3 mRNA levels were not correlated with altered growth. We postulate that IGFBP-5 positively modulates the anabolic effects induced by exogenous IGF-I in the jejunum.
Yang
H
H
Department of Biochemistry, University of Texas Health Science Center at San Antonio, 78284-7760, USA.
Ney
D M
DM
Peterson
C A
CA
Lo
H C
HC
Carey
H V
HV
Adamo
M L
ML
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D019382:Human Growth Hormone / Q000378:metabolism; D007263:Infusions, Parenteral; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics
D002352:Carrier Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein