Overexpression of growth hormone affects alternatively spliced IGF-I mRNA expression in oMt1a-oGH transgenic mice.
Restorative growth hormone (GH) treatment of hypophysectomized rats differentially enhances the transcription of alternative IGF-I mRNA classes in liver. The goal of the present study was to determine the effects of GH overexpression on various classes of hepatic IGF-I mRNA in GH transgenic mice. Unstimulated oMt1a-oGH transgenic mice had low levels of transgene expression, and therefore were used to determine the effects of long-term, slightly elevated GH levels on the abundance on each alternative IGF-I mRNA class. The acute effects of high GH levels on the expression of alternative IGF-I mRNA were studied by gavaging transgenic mice with 25 mM zinc sulfate to activate oMt1a-oGH transgene expression. Long-term, low levels of oGH transgene expression in unstimulated transgenic mice resulted in a 73% down regulation of IGF-I 2Ea mRNA but not 1Ea and 2Eb mRNA. Acute stimulation of transgene expression triggered a rapid, 240% increase in 1Ea mRNA levels within 4 hours of transgene expression while 2Ea mRNA was down regulated to nearly non-detectable levels by 6 hours. IGF-I 2Eb mRNA was not affected by the short-term GH elevation. Our results showed that IGF-I 1Ea and 2Ea mRNA were differentially regulated by chronic low or acute high levels of GH. These results suggest that the regulation of IGF-I 1Ea and 2Ea mRNA transcription involve different postreceptor molecules and/or feedback mechanisms.
Lin
W W
WW
Department of Animal Science, University of California, Davis 95616, USA.
Murray
J D
JD
Oberbauer
A M
AM
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D005246:Feedback; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012756:Sheep
D017931:DNA Primers; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone