|LIN, SHUDAI - South China Agricultural University|
|Li, Congjun - Cj|
|ZHANG, XIQUAN - South China Agricultural University|
Submitted to: International Journal of Molecular Sciences
Publication Type: Review Article
Publication Acceptance Date: 5/7/2018
Publication Date: 5/10/2018
Citation: Lin, S., Li, C., Li, C.Z., Zhang, X. 2018. Growth hormone receptor mutations related to individual dwarfism. International Journal of Molecular Sciences. 19(5):1433. https://doi.org/10.3390/ijms19051433.
Technical Abstract: Growth hormone (GH) promotes body’s growth through binding with two receptors (GHRs) at the cell surface to interact with Janus kinase and signal transducers and activators of transcription, and then to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, the disorder transaction in the GH-GHR-IGF1 axis would course animals’ dwarf. For example, the events of GH could not successfully recognize or/and bind GHR, or GHR fails to transact the GH signal to IGF1 would result in GH dysfunction. The goal of this review focuses on the mutations of GHR which lead to failure of GH-GHR-IGF1 signals transaction process in the dwarf phenotype. Up till now, more than 90 mutations of GHR relevant to short human stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four defects in GHR associated with chicken dwarf have been described. Among 93 mutations of human GHR, 68 are located in the extracellular domain, two occurs in transmembrane domain, 11 are in the intracellular domain of GHR and 12 are in GHR introns. These mutations could interfere with GH-GHR interaction, GHR dimerization, downstream signaling, even in the expression of GHR to make an aberrant function in the GH-GHR-IGF1 axis, resulting in defects in the number and diameter of muscle fibers as well as the bone development.