Alterations in the growth hormone/insulin-like growth factor I pathways in feline GM1 gangliosidosis.
Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted growth, and premature death. Although increased membrane GM1 gangliosides can result in increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I (IGF-I) are important hormonal peptides supporting thymic function and affecting growth throughout the body, particularly in the prepubescent period, several components of the GH/IGF-I pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGF-binding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1 mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats, indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that alterations are external to the liver.
Cox
N R
NR
Scott-Ritchey Research Center, Auburn University College of Veterinary Medicine, Alabama 36849, USA. coxnanc@vetmed.auburn.edu
Morrison
N E
NE
Sartin
J L
JL
Buonomo
F C
FC
Steele
B
B
Baker
H J
HJ
D000375:Aging; D000818:Animals; D002415:Cats; D005677:G(M1) Ganglioside / Q000235:genetics; D016537:Gangliosidosis, GM1 / Q000378:metabolism / Q000662:veterinary*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D005677:G(M1) Ganglioside; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone