title: Serum IGF-I is not a reliable pharmacodynamic marker of exogenous growth hormone activity in mice.
abstract: 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.
authors.affiliation: Endocrine Research Unit, Medizinische Klinik-Innenstadt, Ludwig-Maximilians University, D-80336 Munich, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bielohuby
authors.forename: Michael
authors.initials: M
authors.lastname: Schaab
authors.forename: Moritz
authors.initials: M
authors.lastname: Kummann
authors.forename: Mandy
authors.initials: M
authors.lastname: Sawitzky
authors.forename: Rolf
authors.initials: R
authors.lastname: Gebhardt
authors.forename: Gerhard
authors.initials: G
authors.lastname: Binder
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
authors.forename: Juergen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Martin
authors.initials: M
authors.lastname: Bidlingmaier
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010599:Pharmacokinetics; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I