Dexamethasone-induced abnormalities in growth and bone metabolism in piglets are partially attenuated by growth hormone with no synergistic effect of insulin-like growth factor-I.
Dexamethasone (DEX) therapy improves pulmonary compliance in premature infants with chronic lung disease; however, normal growth and bone development are impaired. Because DEX may mediate its effects by altering the GH-IGF-I axis, we investigated whether adjunctive therapy with GH or GH + IGF-I during DEX therapy could attenuate these DEX-induced effects. Piglets were randomized to placebo, oral tapered DEX (0.5, 0.3, and 0.2 mg kg(-1) d(-1) over 14 d), DEX + GH (0.1 mg kg(-1) d(-1)) or DEX + GH + IGF-I (0.1 mg kg(-1) d(-1)). Final whole body weight and length were improved with GH or GH + IGF-I compared with the DEX alone group. Plasma GH and IGF-I were not influenced by DEX, but infusion of IGF-I resulted in higher (p < 0.05) plasma IGF-I compared with all other groups at d 15. DEX reduced (p < 0.05) circulating IGFBP-2 and IGFBP-3 and liver IGFBP-2 and IGFBP-4 mRNA expression compared with controls. Treatment with DEX alone resulted in lower (p < 0.05) plasma osteocalcin, urinary N-telopeptide, and whole body and femur bone mineral density compared with controls, whereas results with piglets receiving adjunctive GH or GH + IGF-I were similar to those of controls. Given adjunctively, GH alone appears to partially counter the abnormalities in growth and bone metabolism associated with DEX therapy; however, this improvement cannot be attributed to higher circulating IGF-I, because combined therapy did not further improve growth or bone homeostasis compared with DEX + GH treatment. Growth hormone therapy has the potential to stimulate growth in infants exposed to steroid treatment.
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
W E
WE
Ward
S M
SM
Donovan
S A
SA
Atkinson
D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000633:toxicity*; D004347:Drug Interactions; D004357:Drug Synergism; D005938:Glucocorticoids / Q000633:toxicity*; D006130:Growth Disorders / Q000139:chemically induced* / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D005938:Glucocorticoids; D018971:Insulin-Like Growth Factor Binding Protein 2; D018974:Insulin-Like Growth Factor Binding Protein 4; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone