Growth hormone receptor (GHR) (GHR)

The growth hormone receptor (GHR) is a transmembrane protein belonging to the type I cytokine receptor superfamily and serves as the primary mediator for the actions of growth hormone (GH), also known as somatotropin [1, 13]. It is widely expressed in human tissues, with the highest concentration found in the liver, where its activation drives the synthesis of insulin-like growth factor 1 (IGF-1), a key mediator of systemic growth [7, 18]. Upon binding of its ligand, the GHR undergoes a conformational shift and functional dimerization, leading to the activation of associated Janus kinase 2 (JAK2) and the subsequent phosphorylation of STAT transcription factors [14, 18]. These signaling pathways are critical for postnatal longitudinal bone growth, lean muscle mass maintenance, and the regulation of protein, lipid, and carbohydrate metabolism [14, 18].\n\nDysregulation of the GHR is central to several endocrine disorders, including acromegaly, which results from excessive GH-induced receptor activity, and Laron syndrome, a form of dwarfism caused by GHR insensitivity or mutations [3, 12]. In the pharmaceutical industry, the receptor is targeted by both agonists and antagonists; for instance, recombinant growth hormone (somatropin) is used to treat growth deficiencies, while the GHR antagonist pegvisomant is utilized to manage acromegaly by blocking GH binding and reducing pathological IGF-1 levels [7, 12]. Furthermore, emerging research highlights the GHR's involvement in oncology, where it may promote the proliferation and survival of various cancer types, making it a subject of interest for targeted cancer therapies [3, 18]. The input name 'Growth-promoting hormones' is considered incorrect as it refers to a generic category of hormones rather than a specific molecular target [4, 6, 15].

Other names

Somatotropin receptorGH receptorGrowth hormone-binding proteinGHBP

Drugs targeting this pathway function by either mimicking or blocking the activity of growth hormone at its receptor. Agonists, such as recombinant human growth hormone (somatropin) and its long-acting derivatives, bind to the growth hormone receptor and induce functional dimerization. This activation recruits Janus kinase 2 (JAK2), leading to the phosphorylation of the receptor and signal transducers and activators of transcription (STAT5), which promotes the expression of insulin-like growth factor 1 (IGF-1) and other growth-related genes. Conversely, antagonists like pegvisomant bind to the receptor's first binding site but prevent the conformational shift or secondary binding required for functional dimerization, thereby inhibiting downstream signaling and lowering systemic IGF-1 levels in hypersecretory states.