Upper airway loading induces growth retardation and change in local chondrocyte IGF-I expression is reversed by stimulation of GH release in juvenile rats.
Chronic resistive airway loading (CAL) impairs growth in juvenile rats. The effects of CAL on epiphyseal growth plate (EGP) structure and insulin-like growth factor (IGF)-I gene expression have not been explored. Little is known about whether stimulants of endogenous growth hormone (GH) secretion can normalize this growth impairment. This study explored the effect of CAL on circulating and EGP GH/IGF-I pathway GH and the effect of ritanserin (endogenous GH stimulant) on somatic growth and the GH/IGF-I axis. We hypothesized that CAL would lead to a decrease in body temperature (Tb) and alterations of GH/IGF-I pathways, consequently leading to growth retardation. The tracheae of 22-day-old male rats were obstructed by tracheal banding (38 sham-operated control, 42 CAL). Tibial EGP morphometry, liver and EGP IGF mRNA, and serum GH and IGF-I levels were analyzed with quantitative real-time PCR and ELISA. Tb and locomotion activity (MA) were measured with telemetric transmitters inserted into the abdominal cavity. CAL animals had lower Tb and MA despite preserved food consumption. CAL impaired both tibial and tail length gains. Tail and tibial length gains inversely correlated with tracheal resistance. Circulating GH and IGF-I, liver and EGP IGF-I mRNA, and EGP width were decreased in the CAL group. Ritanserin administration to CAL animals normalized circulating and local EGP GH and IGF-I levels and minimized the longitudinal growth impairment. We conclude that CAL causes growth delay associated with alterations in the GH/IGF-I axis. Stimulation of GH release by ritanserin restored both global and local GH/IGF-I pathways, yet growth parameters were only partially restored.
Segev
Yael
Y
Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 105, Beer-Sheva 84105, Israel. yaelse@bgu.ac.il
Berdugo-Boura
Nilly
N
Porati
Orit
O
Tarasiuk
Ariel
A
D000403:Airway Resistance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors; D014132:Trachea / Q000503:physiopathology* / Q000601:surgery
D016713:Ritanserin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone