Histopathology associated with elevated levels of growth hormone and insulin-like growth factor I in transgenic mice.
Serum levels of GH and insulin-like growth factor I (IGF-I) were genetically increased to investigate the physiological activities of these proteins. Lines of mice expressing chimeric genes composed of bovine GH, human GRF, or human IGF-I coding sequences fused to the mouse metallothionein I promoter were examined for consequences of chronic exposure to high levels of these peptides. Animals with elevated serum levels of GH (either bovine GH or mouse GH) have selective splanchnomegaly coupled with glomerular sclerosis and hepatocellularmegaly. Serum levels of insulin and cholesterol are increased. In contrast (with the exception of selective enlargement of organs), the chronic expression of IGF-I results in a different pattern of abnormalities. These findings suggest that the pathogenesis of GH-related disorders is not mediated solely by IGF-I.
Quaife
C J
CJ
Department of Biochemistry, University of Washington, Seattle 98195.
Mathews
L S
LS
Pinkert
C A
CA
Hammer
R E
RE
Brinster
R L
RL
Palmiter
R D
RD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000097:blood / Q000235:genetics / Q000502:physiology*; D006965:Hyperplasia; D006984:Hypertrophy; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008099:Liver / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000473:pathology; D013002:Somatomedins / Q000502:physiology*; D013154:Spleen / Q000473:pathology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D001798:Blood Proteins; D007328:Insulin; D013002:Somatomedins; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002784:Cholesterol