Growth Hormone Receptor

The growth hormone receptor (GHR) is believed to be required for all of the growth promoting and metabolic activities of growth hormone (GH). The GHR is widely expressed among species and is a single membrane-spanning receptor in the cytokine receptor superfamily. GH-induced homodimerization of the GHR causes activation of the receptor-associated cytoplasmic tyrosine kinase JAK2. Multiple signaling pathways, including the STAT, MAP kinase, and PI-3 kinase pathways are downstream of GH-induced JAK2 activation and have been linked to expression of GH-activated genes and GH-induced alterations in cell behavior. STAT5b, in particular, has been shown to mediate important sexually dimorphic effects of GH that correlate with the pulsatile pattern of GH release from the pituitary gland. Clinical disorders arising from deficient or excessive GH action are well described and in some instances are related to aspects of GHR function and/ or can be pharmacologically approached based on the accumulated knowledge concerning the GH-GHR interaction. GHBP, a high-affinity circulating GH-binding protein corresponding to the GHR extracellular domain, arises in some species by alternative RNA splicing and in others by proteolytic shedding from the full-length GHR. GHBP's significance in GH physiology and signaling is as yet unclear.