Regulation of IGF-I mRNA by GH: putative functions for class 1 and 2 message.
This study investigated mechanisms regulating hepatic insulin-like growth factor (IGF)-I class 1 and 2 mRNA levels. Lambs were treated with growth hormone (GH) either as an acute, single dose or over a longer term. Total hepatic unspliced, pre-mRNA levels increased after the single dose of GH but were attenuated after 8 days of GH, with exon 1- and 2-derived pre-mRNA levels displaying coordinate responses. Surprisingly, changes in total spliced, mature mRNA levels did not reflect those for pre-mRNA, instead being augmented after 8 days of GH. GH also induced a differential increase in the ratio of mature class 2-to-class 1 IGF-I mRNA; therefore, this must be predominantly via posttranscriptional mechanisms. Increases in the ratio of class 2-to-class 1 mRNA were observed in polysomal vs. total RNA preparations derived from GH-treated but not control lambs, indicating an increased proportion of class 2 transcripts engaged in translation. Our findings indicate that GH may stabilize mature class 2 transcripts or destabilize mature class 1 transcripts and that class 2 mRNA may have a greater translational potential. The following two main functions of hepatic class 2 IGF-I mRNA are suggested: an efficient "monitor" of GH status via providing a rapid negative feedback mechanism and a coordinator of endocrine-regulated tissue growth.
O'Sullivan
D C
DC
The Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Szestak
T A M
TA
Pell
J M
JM
D000818:Animals; D000831:Animals, Newborn; D001769:Blood / Q000378:metabolism; D004334:Drug Administration Schedule; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009994:Osmolar Concentration; D011132:Polyribosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000145:classification / Q000378:metabolism*; D012016:Reference Values; D012756:Sheep
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone