Genetic dissection of IGF1-dependent and -independent effects of permanent GH excess on postnatal growth and organ pathology of mice

•Effects of GH and IGF1 can be dissected in GH transgenic Igf1 knockout mice in vivo.•Permanent GH overabundance cannot reverse Igf1 deletion related dwarfism in mice.•Kidney and liver alterations of GH transgenic mice can develop independently of IGF1.

To study insulin-like growth factor 1 (IGF1)-independent effects of permanent growth hormone (GH) excess on body and organ growth and pathology in vivo, hemizygous bovine GH transgenic mice with homozygous disruption of the Igf1 gene (Igf1−/−/GH) were generated, and examined in comparison to Igf1−/−, Igf1+/−, wild-type (WT), Igf1+/−/GH, and GH mice. GH mice and Igf1+/−/GH mice showed increased serum IGF1 levels and the well-known giant-phenotype of GH transgenic mice. In contrast, the typical dwarf-phenotype of Igf1−/− mice was only slightly ameliorated in Igf1−/−/GH mice. Similar to GH mice, Igf1−/−/GH mice displayed hepatocellular hypertrophy, glomerulosclerosis, and reduced volumes of acidophilic cells in the pituitary gland. However, GH excess associated skin lesions of male GH mice were not observed in Igf1−/−/GH mice. Therefore, development of GH excess induced liver-, kidney-, and pituitary gland-alterations in GH transgenic mice is independent of IGF1 whereas GH stimulated body growth depends on IGF1.