GH receptor

For patients treated with a GH receptor antagonist, GH levels are not measured because pegvisomant is a modified GH molecule that is detected in commercial GH assays, resulting in falsely... 

Growth hormone (GH) GH receptor Extracellular domain Monomeric 1 2... 

FIGURE 4.3 Growth hormone receptor. Monomeric GH associates with two receptor monomers. Activated JAK2 kinases /ram-phosphorylatc JAK2 and GH receptors, and STAT transcription factors are phosphorylated by JAK2. 

Although ubiquitin-conjugation of receptors in mammalian cells has been observed, the function of this modification seems less clear. In the case of the growth hormone receptor (GH-receptor) and the epithelial Na-t- channel (ENaC), it seems likely that ubiquitin-conjugation triggers their endocytosis. 

A small number of children with growth failure have severe IGF-1 deficiency that is not responsive to exogenous GH. Causes include mutations in the GH receptor and development of neutralizing antibodies to GH. In 2005, the FDA approved mecasermin for treatment of severe IGF-1 deficiency that is not responsive to GH. Mecasermin is a complex of recombinant human IGF-1 (rhIGF-1) and recombinant human insulin-like growth factor-binding protein-3 (rhIGFBP-3). 

Pegvisomant is a GH receptor antagonist that is useful for the treatment of acromegaly. Pegvisomant is the polyethylene glycol (PEG) derivative of a mutant GH, B2036, which has increased affinity for one site of the GH receptor but a reduced... 

Pegvisomant Blocks GH receptors Ameliorates effects of excess GH production Acromegaly SC injection 3-7 x/wk Toxicity Increased liver enzymes... 

IGF-1 can have all the side effect of GH or insulin use with an added negative gastrointestinal (GI) growth. This is due to a higher number of IGF-1 receptors being located in the GI tract as compared to skeletal muscle. The latter has more GH receptors. This explains much of the bloat seen in pro bodybuilders of late. 

C. Eschen, J. Nowak, and K. Poulsen. 1994. Studies on the renal kinetics of growth hormone (GH) and on the GH receptor and related effects in animals. 

Although there has been emphasis on rabbit liver, GH receptors have been studied in liver from many other species and in many other tissues and cultured cell lines [17,18]. The human lymphocyte-derived cell line, IM9, has provided a useful source, though the physiological significance of binding of GH to these cells is not clear. The binding and structural properties of GH receptors vary considerably according to the tissue and species from which they are derived. 

Fig. 3. Cross-linking of l25I-labelled human GH to rabbit liver receptors. Labelled GH was incubated with receptors, cross-linked with disuccinimidyl suberate and then subjected to SDS polyacrylamide gel electrophoresis. 1. Total binding 2-4. Displacement with 1 fig unlabelled human GH, bovine GH and ovine prolactin respectively 5. l25I-human GH without receptors. Note the major GH-receptor complex of M, = 80000 (indicating a receptor protein or subunit of Af, 58000) and various other components of larger and smaller M,.

Cross-linking has also been used to detect GH receptors/binding sites in other tissues and species. The main receptor component detected in rat liver and the human IM9 cell line (which binds human GH specifically) is rather larger (Mt = 100000) than that seen in rabbit liver [35,37], Multiple cross-linked GH-receptor components have been detected in rat hepatocytes, but these are probably all related to aggregates of glycoprotein subunits of Mr 100000 held together by disulphide bonds and non-covalent interactions [37]. 

Partial purification of membrane-bound GH receptors from rabbit liver has been achieved after solubilization with detergents [36,38]. Affinity chromatography on immobilized GH or lectins proved a particularly powerful way of isolating the receptors. However, antibodies raised against the partially-purified receptors failed to block the growth-promoting actions of the hormone. 

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