Overexpression of growth hormone affects alternatively spliced IGF-I mRNA expression in oMt1a-oGH transgenic mice

Restorative growth hormone (GH) treatment of hypophysectomized rats differe ntially enhances the transcription of alternative IGF-I mRNA classes in liv er. The goal of the present study was to determine the effects of GH overex pression on various classes of hepatic IGF-I mRNA in GH transgenic mice. Un stimulated oMtla-oGH transgenic mice had low levels of transgene expression , and therefore were used to determine the effects of longterm, slightly el evated GH levels on the abundance of each alternative IGF-I mRNA class. The acute effects of high GH levels on the expression of alternative IGF-I mRN A were studied by gavaging transgenic mice with 25 mM zinc sulfate to activ ate oMtla-oGH transgene expression. Long-term, low levels of oGH transgene expression in unstimulated transgenic mice resulted in a 73% down regulatio n of IGF-I 2Ea mRNA but not 1Ea and 2Eb mRNA. Acute stimulation of transgen e expression triggered a rapid, 240% increase in 1Ea mRNA levels within 4 h ours of transgene expression while 2Ea mRNA was down regulated to nearly no n-detectable levels by 6 hours. IGF-I 2Eb mRNA was not affected by the shor t-term GH elevation. Our results showed that IGF-I 1Ea and 2Ea mRNA were di fferentially regulated by chronic low or acute high levels of GH. These res ults suggest that the regulation of IGF-I 1Ea and 2Ea mRNA transcription in volve different postreceptor molecules and/or feedback mechanisms.