New molecular mechanisms of GH resistance

Primary growth hormone (GH) resistance describes growth failure in the presence of normal, or even elevated, GH secretion. In its classic form, the phenotype is identical to that of GH deficiency, and was originally described in association with defects of the GH receptor. With increasing understanding of the GH-insulin-like growth factor (IGF) axis, it has become apparent that GH resistance can result from either primary IGF deficiency (IGFD) or IGF resistance. Primary IGFD may be due to: (i) defects of the GH receptor, (ii) defects of post-GH receptor signaling or (iii) primary defects of IGF-I synthesis. IGF resistance may result from: (i) defects of the IGF receptor, (ii) defects of post-IGF receptor signaling, (iii) defects of IGF binding proteins or (iv) defects of the epiphyseal growth plate or of regulatory proteins involved in epiphyseal growth.