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Growth cartilage expression of growth hormone/insulin-like growth factor I axis in spontaneous and growth hormone induced catch-up growth
Authors:Iva Brito  Helena Gil-Peña  Inés Molinos  Vanessa Loredo  Tiago Henriques-Coelho  Alberto Caldas-Afonso  Fernando Santos
Affiliation:1. Pediatric Rheumatology Unit, Pediatric Department, Hospital São João, Porto, Portugal;2. Physiology and Cardiothoracic Surgery Department, Faculty of Medicine, Porto, Portugal;3. Department of Pediatrics, Hospital Universitario Central de Asturias and University of Oviedo, Oviedo, Asturias, Spain;4. Department of Pediatrics, Hospital São João, Porto, Portugal
Abstract:IntroductionCatch-up growth following the cessation of a growth inhibiting cause occurs in humans and animals. Although its underlying regulatory mechanisms are not well understood, current hypothesis confer an increasing importance to local factors intrinsic to the long bones' growth plate (GP).AimThe present study was designed to analyze the growth-hormone (GH)-insulin-like growth factor I (IGF-I) axis in the epiphyseal cartilage of young rats exhibiting catch-up growth as well as to evaluate the effect of GH treatment on this process.Material and methodsFemale Sprague–Dawley rats were randomly grouped: controls (group C), 50% diet restriction for 3 days + refeeding (group CR); 50% diet restriction for 3 days + refeeding &; GH treatment (group CRGH). Analysis of GH receptor (GHR), IGF-I, IGF-I receptor (IGF-IR) and IGF binding protein 5 (IGFBP5) expressions by real-time PCR was performed in tibial growth plates extracted at the time of catch-up growth, identified by osseous front advance greater than that of C animals.ResultsIn the absence of GH treatment, catch-up growth was associated with increased IGF-I and IGFBP5 mRNA levels, without changes in GHR or IGF-IR. GH treatment maintained the overexpression of IGF-I mRNA and induced an important increase in IGF-IR expression.ConclusionsCatch-up growth that happens after diet restriction might be related with a dual stimulating local effect of IGF-I in growth plate resulting from overexpression and increased bioavailability of IGF-I. GH treatment further enhanced expression of IGF-IR which likely resulted in a potentiation of local IGF-I actions. These findings point out to an important role of growth cartilage GH/IGF-I axis regulation in a rat model of catch-up growth.
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