The GH/IGF-1 Axis: Insights from Animal Models

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Individuals develop from single cells through a genetically controlled program that regulates cell growth, cell proliferation and differentiation. The quantitative equilibrium between cell differentiation and proliferation is particularly important for tissue-specific growth and the shaping of higher organisms. Insulin-like growth factors (IGF) are key regulators of somatic growth, and growth hormone (GH), by controlling important aspects of IGF activity in many tissues in mammals, is able to coordinate this growth in a defined, spatio-temporal manner at the whole body level. Using homologous recombination, we generated mouse models with genetically determined IGF-1R insufficiency. We showed that partial inactivation of IGF-1R causes postnatal growth deficits that appear during the postnatal growth spurt and persist in the adult. We found that these growth deficits depend on the dosage of the IGF-1R gene. In our mutant mice, the postnatal growth of males relied more strongly on IGF-1R levels than the growth of females. Experiments using tissue-specific IGF-1R inactivation in the central nervous system provided evidence that IGF signaling in the brain may play a key role during the development of the somatotrope function in mammals.