The effect of dexamethasone on body and organ growth of normal and IGF-II-transgenic mice.
The physiological role of IGF-II remains unclear but there is evidence for a role in postnatal growth, the growth of the thymus and bone homeostasis. Glucocorticoids have many effects that are opposite to the effects of IGF-II such as growth retardation, osteoporosis and thymic involution. We therefore wondered whether IGF-II overexpression in transgenic mice might counteract some of the growth inhibitory effects of the glucocorticoid, dexamethasone (DXM). In a dose-finding study in normal mice, 20 microg DXM/day caused a significant growth delay. The various organs had a different susceptibility to the growth inhibitory effects of DXM. Most affected were thymus and spleen, followed by liver, skeletal muscle and lumbar vertebrae. The weights of the kidney, tibia, and humerus were not significantly diminished. In a second experiment, the effects of DXM in normal and IGF-II-transgenic animals were compared. The IGF-II serum levels in the transgenic animals were more than 40-fold increased compared with control mice and were decreased by 35% in the DXM-treated group. IGF-I serum levels were identical in both mouse strains and rose slightly after DXM administration in controls. Transgenic mice had higher levels of IGF binding protein species of apparent molecular masses of 41.5 kDa, 30 kDa, and 26.5 kDa. DXM reduced the 24 kDa band in both mice strains. In addition it reduced the bands at 38.5 kDa and 26.5 kDa but only in the transgenic animals. The effect of DXM on body growth was similar in normal and IGF-II-transgenic mice. The weight reduction of the various organs caused by DXM was similar in both types of mice except for the skeleton. The weight of the tibia and the humerus were significantly higher in the DXM-treated transgenic mice. In conclusion, we speculate that overexpression of IGF-II in mice partially protects bone from the osteopenic effects of glucocorticoids.
Rooman
R
R
Department of Pediatrics, Wilhelmina Children's Hospital, Utrecht University, The Netherlands.
Koster
G
G
Bloemen
R
R
Gresnigt
R
R
van Buul-Offers
S C
SC
D000818:Animals; D015153:Blotting, Western; D001824:Body Constitution; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006132:Growth Plate / Q000187:drug effects*; D006811:Humerus / Q000187:drug effects; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013977:Tibia / Q000187:drug effects
D005938:Glucocorticoids; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone