Genetic increase in serum insulin-like growth factor-I (IGF-I) in C3H/HeJ compared with C57BL/6J mice is associated with increased transcription from the IGF-I exon 2 promoter.
C3H/HeJ (C3H) mice exhibit 30-40% higher serum IGF-I than do C57BL/6J (B6) mice, in association with increased bone mineral density and strength. These differences are inherited and thus provide a model for determining molecular mechanisms for genetic variation of serum IGF-I and downstream actions. We now report that increased serum IGF-I in C3H mice is associated with increased transcription from the minor exon 2 promoter in liver from female and male mice. The increase in hepatic IGF-I gene expression caused by increased abundance of IGF-I mRNA transcribed from the exon 2 promoter can quantitatively account for the increased serum IGF-I in C3H mice. Also, levels of both Ea and Eb IGF-I mRNAs are increased in livers of male C3H mice. Fasting lowered serum IGF-I and liver IGF-I mRNA levels in female mice of both strains. However, serum IGF-I and liver IGF-I mRNA levels remained higher in fasted C3H mice compared with fasted B6 mice. Levels of IGF-I transcripts initiated from exon 2 are also significantly increased in skeletal muscle, fat, ovaries, and kidneys of C3H mice. IGF binding protein (IGFBP)-5 mRNA levels are significantly higher in muscle and fat of C3H mice than in B6 mice. Levels of exon 1-containing transcripts are increased in whole femurs of male and female C3H mice. We conclude that increased transcription of the IGF-I gene occurs in a promoter- and tissue-specific manner in C3H mice. The increased IGF binding protein-5 mRNA levels in fat and muscle suggest that IGF-I signaling is increased in these tissues in C3H mice.
Adamo
Martin L
ML
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. adamo@biochem.uthscsa.edu
Ma
Xiuye
X
Ackert-Bicknell
Cheryl L
CL
Donahue
Leah Rae
LR
Beamer
Wesley G
WG
Rosen
Clifford J
CJ
D000818:Animals; D005091:Exons; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013045:Species Specificity; D014158:Transcription, Genetic
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone