miRNA as a Growth Plate Marker After GH

The therapeutic use of recombinant human growth hormone usually determines adequate growth response in the majority of approved conditions. However, it is well recognized an inter-individual responsiveness, and the classical biomarker such as GH peak response, IGF-I or IGFBP3 levels have poor correlation with clinical outcome. We hypothesize that markers directed originated from the growth plate would have the potential to better correlate with growth response during GH treatment. Genetic markers, as the growth hormone receptor exon 3-deletion polymorphism, IGFBP3 polymorphisms were previously tested in an attempt to discriminate the pattern of responsiveness, but results were contradictory in the different studies. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Due to their ability to regulate gene expression, miRNAs play an important role both in physiology and pathophysiological conditions, and also an important role in the regulation of endochondral ossification and regulation of the hypothalamic-pituitary-IGF axis. Several miRNAs are already recognized as involved in the regulation of longitudinal growth and bone development, through its action upon WNT-βcatenin, Notch, PI3K/AKT and TGFβ signaling pathways. AIM: Therefore, the aim of this study is to establish a panel of miRNAs correlated to the growth response during GH treatment, that can be used of biomarker for early recognition and classification of patients according to GH therapy responsiveness. This study will analyze 30 Children and adolescents with GH deficiency associated with Ectopic Posterior Pituitary (EPP) gland. METHODS: Clinical, biochemical and miRNAs concentration will be measured at four time-points: before starting therapy (basal), and after 1-, 3- and 6-months during GH treatment. Studied variables include: height, target height, growth velocity and body mass index, bone age and pubertal stage. Laboratory Assessment: at basal condition: fasting glucose, insulin