Involvement of the skeletal GH-IGF system in an experimental model of diabetes-induced growth retardation.
Uncontrolled diabetes is associated with growth retardation. We investigated the effect of insulin-dependent diabetes on animal growth and IGF-I gene expression in the epiphyseal growth plate region of the long bones. We also studied the effect of GH administration on somatic growth in the diabetic state. Streptozotocin (STZ)-injected diabetic rats had a decreased somatic growth rate in comparison to controls. GH administration (2.5 U/kg day) in the diabetic animals (DGH group) prevented this decrease. Serum IGF-I levels were decreased in both diabetic and DGH animals. Within 72 h from diabetes onset, IGF-I mRNA levels in epiphyseal growth plate homogenates decreased whereas IGF-I receptor mRNA levels increased in diabetic animals. The decrease in IGF-I mRNA transcript levels was localized to the metaphyseal region by in situ hybridization. We conclude that in the STZ-induced diabetic state, the reduction in linear growth is associated with a parallel decrease in IGF-I gene expression at the epiphyseal growth plate area. Diabetic growth retardation can be reversed with GH administration, which does not reconstitute serum IGF-I levels. Therefore, we speculate that GH in this model may act locally through the skeletal GH-IGF-I system.
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Y
Y
Segev
D
D
Landau
S
S
Davidoff-Friedman
M
M
Weinreb
M
M
Phillip
D000818:Animals; D001769:Blood / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism*; D006130:Growth Disorders / Q000209:etiology*; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D006132:Growth Plate / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000235:genetics; D013002:Somatomedins / Q000378:metabolism*
D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1