Mette Bjerre

Serum IGF-I is not a reliable pharmacodynamic marker of exogenous growth hormone activity in mice

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Maximilian Bielohuby
  • ,
  • Michael Schaab
  • ,
  • Moritz Kummann
  • ,
  • Mandy Sawitzky
  • ,
  • Rolf Gebhardt
  • ,
  • Gerhard Binder
  • ,
  • Jan Frystyk
  • Mette Bjerre
  • Andreas Hoeflich
  • ,
  • Juergen Kratzsch
  • ,
  • Martin Bidlingmaier
Serum IGF-I is a well-established pharmacodynamic marker of GH administration in humans and has been used for this purpose in animal studies. However, its general suitability in wild-type laboratory mice has not been demonstrated. Here we show that treatment with recombinant human GH (rhGH) in four different strains of laboratory mice increases body weight, lean body mass, and liver weight but does not increase hepatic expression and release of IGF-I. In contrast and as expected, hypophysectomized rats show a rapid increase in serum IGF-I after rhGH administration. The lack of IGF-I up-regulation in mice occurs despite hepatic activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and is not explained by GH dose, route of administration, origin of GH (i.e. recombinant human, bovine, and murine GH), treatment duration, genetic background, sex, or formation of neutralizing antibodies. Effects on other components of the GH/IGF pathway were highly influenced by genetic background and sex but not consistently affected by rhGH treatment. We conclude that IGF-I is not a reliable indicator of the biological effects of exogenous GH treatment in genetically and pharmacologically unmodified mice. We speculate that IGF-I release is already maximal in these animals and cannot be further increased by exogenous GH treatment. This is also suggested by the observation of restored IGF-I up-regulation in isolated murine hepatocytes after rhGH treatment. Total body weight, lean body mass, and liver weight may be more reliable phenotypic indicators in these models.
OriginalsprogEngelsk
BogserieContemporary Endocrinology
Vol/bind152
Nummer12
Sider (fra-til)4764-76
Antal sider13
ISSN0196-8653
DOI
StatusUdgivet - 2011

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