somatotropin receptors


Summary: Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins.

Top Publications

  1. Sotiropoulos A, Ohanna M, Kedzia C, Menon R, Kopchick J, Kelly P, et al. Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation. Proc Natl Acad Sci U S A. 2006;103:7315-20 pubmed
    ..Taken together, these data unravel a specific function of GH in the control of cell fusion, an essential process for muscle growth. ..
  2. Robertson K, Kopchick J, Liu J. Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice. Am J Physiol Endocrinol Metab. 2006;291:E491-8 pubmed
    ..These data demonstrate that GH signaling is not required for compensatory islet growth. Thus, in both muscle insulin responsiveness and islet growth compensation, normal levels of GH signals do not seem to play a dominant role. ..
  3. Li M, Raine J, Leatherland J. Expression profiles of growth-related genes during the very early development of rainbow trout embryos reared at two incubation temperatures. Gen Comp Endocrinol. 2007;153:302-10 pubmed
    ..0 degrees C compared with the faster developing embryos reared at 8.5 degrees C. The study suggests that the EGTA begins between 2- and 5-dpf, with a staged increase in EGTA between 5- and 13-dpf. ..
  4. Bonkowski M, Pamenter R, Rocha J, Masternak M, Panici J, Bartke A. Long-lived growth hormone receptor knockout mice show a delay in age-related changes of body composition and bone characteristics. J Gerontol A Biol Sci Med Sci. 2006;61:562-7 pubmed
    ..These parameters also continued to increase with age. Our results indicate that GH resistance alters body composition, bone growth, and bone maintenance during aging in GHR-KO mice. ..
  5. David A, Metherell L, Clark A, Camacho Hubner C, Savage M. Diagnostic and therapeutic advances in growth hormone insensitivity. Endocrinol Metab Clin North Am. 2005;34:581-95, viii pubmed
  6. Bonkowski M, Rocha J, Masternak M, Al Regaiey K, Bartke A. Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci U S A. 2006;103:7901-5 pubmed
    ..The present findings also support the notion that enhanced sensitivity to insulin plays a prominent role in the actions of CR and GH resistance on longevity. ..
  7. Viitala S, Szyda J, Blott S, Schulman N, Lidauer M, Mäki Tanila A, et al. The role of the bovine growth hormone receptor and prolactin receptor genes in milk, fat and protein production in Finnish Ayrshire dairy cattle. Genetics. 2006;173:2151-64 pubmed
    ..In particular, the GHR F279Y has the highest influence on protein percentage and fat percentage while PRLR S18N markedly influences protein and fat yield. Furthermore, an interaction between the two loci is suggested. ..
  8. Varvio S, Iso Touru T, Kantanen J, Viitala S, Tapio I, Mäki Tanila A, et al. Molecular anatomy of the cytoplasmic domain of bovine growth hormone receptor, a quantitative trait locus. Proc Biol Sci. 2008;275:1525-34 pubmed publisher
    ..Alternative explanations for the persistent polymorphism include balancing selection, hitch-hiking, pleiotropic or sexually antagonistic fitness effects or relaxed functional constraints. ..
  9. Gabillard J, Yao K, Vandeputte M, Gutierrez J, Le Bail P. Differential expression of two GH receptor mRNAs following temperature change in rainbow trout (Oncorhynchus mykiss). J Endocrinol. 2006;190:29-37 pubmed
    ..In juveniles, the GHR, by integrating the effect of temperature on plasma GH and nutritional state, could play a key role in the growth-promoting effect of temperature. ..

More Information


  1. Norbeck L, Kittilson J, Sheridan M. Resolving the growth-promoting and metabolic effects of growth hormone: Differential regulation of GH-IGF-I system components. Gen Comp Endocrinol. 2007;151:332-41 pubmed
  2. Masternak M, Al Regaiey K, Del Rosario Lim M, Jimenez Ortega V, Panici J, Bonkowski M, et al. Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice. Exp Gerontol. 2005;40:679-84 pubmed
    ..The results also show that improved insulin sensitivity in response to CR is not due to increased mRNA expression of the above genes in either normal or GHR-KO animals. ..
  3. Bartke A, Brown Borg H. Life extension in the dwarf mouse. Curr Top Dev Biol. 2004;63:189-225 pubmed
    ..An important role of IGF-1 and insulin in the control of mammalian longevity is consistent with the well-documented actions of homologous signaling pathways in invertebrates. ..
  4. Leung K, Johannsson G, Leong G, Ho K. Estrogen regulation of growth hormone action. Endocr Rev. 2004;25:693-721 pubmed
    ..This represents a novel paradigm of steroid regulation of cytokine receptors and is likely to have significance for a diverse range of cytokine function. ..
  5. Radcliff R, McCormack B, Crooker B, Lucy M. Plasma hormones and expression of growth hormone receptor and insulin-like growth factor-I mRNA in hepatic tissue of periparturient dairy cows. J Dairy Sci. 2003;86:3920-6 pubmed
    ..Rapid changes in placental and ovarian steroids before parturition were coincident with changes in GHR 1A mRNA. ..
  6. Neuvians T, Pfaffl M, Berisha B, Schams D. The mRNA expression of the members of the IGF-system in bovine corpus luteum during induced luteolysis. Domest Anim Endocrinol. 2003;25:359-72 pubmed
    ..There were no significant changes in IGF I mRNA expression. In conclusion, the IGF-system with all its components seems to play an important role in the very complex process of PGF2alpha-induced luteolysis in bovine CL. ..
  7. Cunha K, Barboza E, Da Fonseca E. Identification of growth hormone receptor in localised neurofibromas of patients with neurofibromatosis type 1. J Clin Pathol. 2003;56:758-63 pubmed
    ..Most patients with NF1 have localised neurofibromas that express GHR. This suggests that GH may play some role in the development of localised neurofibromas in patients with NF1. ..
  8. Pershing R, Lucy M, Thatcher W, Badinga L. Effects of BST on oviductal and uterine genes encoding components of the IGF system in lactating dairy cows. J Dairy Sci. 2002;85:3260-7 pubmed
    ..Results indicate complex and tissue-specific regulation of the uterine IGF system components by exogenous bST. Some of those biological responses to bST may be important in early development of bovine embryos. ..
  9. Al Regaiey K, Masternak M, Bonkowski M, Sun L, Bartke A. Long-lived growth hormone receptor knockout mice: interaction of reduced insulin-like growth factor i/insulin signaling and caloric restriction. Endocrinology. 2005;146:851-60 pubmed
    ..These results also add to the evidence that targeted disruption of the GH receptor/GH-binding protein gene and CR act via overlapping, but distinct, mechanisms. ..
  10. Conte F, Salles J, Raynal P, Fernandez L, Molinas C, Tauber M, et al. Identification of a region critical for proteolysis of the human growth hormone receptor. Biochem Biophys Res Commun. 2002;290:851-7 pubmed
    ..Taken together, these results suggest that integrity of the juxtamembrane region of GHR is necessary for its biochemical cleavage and that a common mechanism is involved in constitutive and PMA-induced shedding. ..
  11. Coschigano K, Holland A, Riders M, List E, Flyvbjerg A, Kopchick J. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003;144:3799-810 pubmed
    ..Finally, life span was significantly extended for the GHR -/- mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes. ..
  12. Casse A, Desplanches D, Mayet Sornay M, Raccurt M, Jegou S, Morel G. Growth hormone receptor expression in atrophying muscle fibers of rats. Endocrinology. 2003;144:3692-7 pubmed
    ..The present data suggest that muscle atrophy is associated with a muscle fiber type-specific GHR mRNA up-regulation mechanism that helps protect atrophying fibers in EDL but might be part of an attempt to repair in SOL. ..
  13. Yamaguchi A, Ikeda Y, Hirai T, Fujikawa T, Morita I. Local changes of IGF-I mRNA, GH receptor mRNA, and fiber size in rat plantaris muscle following compensatory overload. Jpn J Physiol. 2003;53:53-60 pubmed
    ..Thus muscle fiber hypertrophy following compensatory overload was different among the parts in a muscle and IGF-I mRNA was expressed in concert with the region-specific hypertrophy, but not GH receptor mRNA. ..
  14. Adkins R, Walton A, Honeycutt R. Higher-level systematics of rodents and divergence time estimates based on two congruent nuclear genes. Mol Phylogenet Evol. 2003;26:409-20 pubmed
    ..However, when a relaxed molecular clock was applied, estimated divergence dates were highly compatible with the fossil record. ..
  15. Blott S, Kim J, Moisio S, Schmidt Küntzel A, Cornet A, Berzi P, et al. Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition. Genetics. 2003;163:253-66 pubmed
  16. Piwien Pilipuk G, Huo J, Schwartz J. Growth hormone signal transduction. J Pediatr Endocrinol Metab. 2002;15:771-86 pubmed
    ..Cross-talk among these signaling cascades in regulating specific genes suggests that GH signaling to the nucleus involves a GH-regulated signaling network. ..
  17. Rowland J, Lichanska A, Kerr L, White M, d Aniello E, Maher S, et al. In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol. 2005;25:66-77 pubmed
    ..These mice represent the first step in delineating the domains of the GHR regulating body growth and composition and the transcripts associated with these domains. ..
  18. Sakamoto K, Komatsu T, Kobayashi T, Rose M, Aso H, Hagino A, et al. Growth hormone acts on the synthesis and secretion of alpha-casein in bovine mammary epithelial cells. J Dairy Res. 2005;72:264-70 pubmed
  19. Li Y, Yuan L, Yang X, Ni Y, Xia D, Barth S, et al. Effect of early feed restriction on myofibre types and expression of growth-related genes in the gastrocnemius muscle of crossbred broiler chickens. Br J Nutr. 2007;98:310-9 pubmed
  20. Jukić Z, Tomas D, Mijic A, Kruslin B. Expression of growth hormone receptor and growth hormone in colorectal carcinoma. Hepatogastroenterology. 2009;56:85-8 pubmed
    ..Patients with increased expression of growth hormone receptor had more common recurrence of the disease and shorter survival. ..
  21. Duckles S, Miller V. Hormonal modulation of endothelial NO production. Pflugers Arch. 2010;459:841-51 pubmed publisher
  22. Adriani M, Garbi C, Amodio G, Russo I, Giovannini M, Amorosi S, et al. Functional interaction of common gamma-chain and growth hormone receptor signaling apparatus. J Immunol. 2006;177:6889-95 pubmed
    ..These data also confirm that growth failure in X-SCID is primarily related to the genetic alteration of the IL2RG gene. ..
  23. Brue T, Castinetti F, Lundgren F, Koltowska Haggstrom M, Petrossians P. Which patients with acromegaly are treated with pegvisomant? An overview of methodology and baseline data in ACROSTUDY. Eur J Endocrinol. 2009;161 Suppl 1:S11-7 pubmed publisher
  24. Sasaki Y, Satoh K, Hayasaki H, Fukumoto S, Fujiwara T, Nonaka K. The P561T polymorphism of the growth hormone receptor gene has an inhibitory effect on mandibular growth in young children. Eur J Orthod. 2009;31:536-41 pubmed publisher
    ..These findings suggest that P561T heterozygous mutation affects mandibular growth during early childhood, and this mutation in the GHR gene is hypothesized to function as an inhibitory factor in the process of mandibular growth. ..
  25. Bianchi A, Giustina A, Cimino V, Pola R, Angelini F, Pontecorvi A, et al. Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab. 2009;94:2015-22 pubmed publisher
    ..Moreover, the d3-GHR isoform could be an independent predictor of GH and IGF-I discrepancy during the follow-up in acromegaly. ..
  26. Metzner C, Hadziselimovic S, Grafe I, Nawroth P, Kasperk C. [Therapeutic management of acromegaly]. Med Klin (Munich). 2006;101:15-23 pubmed
    ..In the absence of a remission there are effective pharmacological treatment regimens available among which somatostatin analogs are recommended as the first-line treatment. ..
  27. Venken K, Schuit F, Van Lommel L, Tsukamoto K, Kopchick J, Coschigano K, et al. Growth without growth hormone receptor: estradiol is a major growth hormone-independent regulator of hepatic IGF-I synthesis. J Bone Miner Res. 2005;20:2138-49 pubmed
    ..E(2) rescues pubertal skeletal growth during GH resistance through a novel mechanism of GHR-independent stimulation of IGF-I synthesis in the liver. ..
  28. Johnson T, Fujimoto B, Jimenez Flores R, Peterson D. Growth hormone alters lipid composition and increases the abundance of casein and lactalbumin mRNA in the MAC-T cell line. J Dairy Res. 2010;77:199-204 pubmed publisher
    ..These results indicate that GH is an important factor in inducing a lactogenic phenotype in the MAC-T cell line, and support the possibility of a direct effect of GH on milk synthesis in vivo. ..
  29. Canosa L, Chang J, Peter R. Neuroendocrine control of growth hormone in fish. Gen Comp Endocrinol. 2007;151:1-26 pubmed
    ..However, more work remains to be done in order to better understand the integrative mechanisms of signal transduction at the somatotrope level and the relevance of various GH regulators in different physiological circumstances. ..
  30. Campbell B, Dickey J, Beckman B, Young G, Pierce A, Fukada H, et al. Previtellogenic oocyte growth in salmon: relationships among body growth, plasma insulin-like growth factor-1, estradiol-17beta, follicle-stimulating hormone and expression of ovarian genes for insulin-like growth factors, steroidogenic-acute regulat. Biol Reprod. 2006;75:34-44 pubmed
  31. Divisova J, Kuiatse I, Lazard Z, Weiss H, Vreeland F, Hadsell D, et al. The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth. Breast Cancer Res Treat. 2006;98:315-27 pubmed
    ..This data supports previous studies indicating a role for GH/IGF in mammary gland development, and suggests that pegvisomant maybe useful for the prevention and/or treatment of estrogen receptor positive breast cancer. ..
  32. Zych S, Szatkowska I, Czerniawska Piatkowska E. [Growth hormone signaling pathways]. Postepy Biochem. 2006;52:367-72 pubmed
    ..Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too. ..
  33. Saera Vila A, Calduch Giner J, Prunet P, Pérez Sánchez J. Dynamics of liver GH/IGF axis and selected stress markers in juvenile gilthead sea bream (Sparus aurata) exposed to acute confinement: differential stress response of growth hormone receptors. Comp Biochem Physiol A Mol Integr Physiol. 2009;154:197-203 pubmed publisher
    ..These results provide suitable evidence for a functional partitioning of hepatic GHRs under states of reduced IGF production and changing cellular environment resulting from acute confinement. ..
  34. Cunha K, Barboza E, Fonseca E. Identification of growth hormone receptor in plexiform neurofibromas of patients with neurofibromatosis type 1. Clinics (Sao Paulo). 2008;63:39-42 pubmed
    ..Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1. ..
  35. Hagemeister A, Sheridan M. Somatostatin inhibits hepatic growth hormone receptor and insulin-like growth factor I mRNA expression by activating the ERK and PI3K signaling pathways. Am J Physiol Regul Integr Comp Physiol. 2008;295:R490-7 pubmed publisher
    ..These results indicate that SS-14-inhibited GHR expression is mediated by the ERK signaling pathway and that the PI3K/Akt pathway mediates, at least in part, SS-14 inhibition of GH-stimulated IGF-I expression. ..
  36. Tomoyasu Y, Yamaguchi T, Tajima A, Nakajima T, Inoue I, Maki K. Further evidence for an association between mandibular height and the growth hormone receptor gene in a Japanese population. Am J Orthod Dentofacial Orthop. 2009;136:536-41 pubmed publisher
    ..This might partly explain the differing craniofacial morphology among different ethnicities. ..
  37. Barclay J, Kerr L, Arthur L, Rowland J, Nelson C, Ishikawa M, et al. In vivo targeting of the growth hormone receptor (GHR) Box1 sequence demonstrates that the GHR does not signal exclusively through JAK2. Mol Endocrinol. 2010;24:204-17 pubmed publisher
    ..This has allowed us for the first time to identify in vivo Src/ERK-regulated transcripts, JAK2-regulated transcripts, and those regulated by the distal part of the GHR, particularly by STAT5. ..
  38. Poger D, Mark A. Turning the growth hormone receptor on: evidence that hormone binding induces subunit rotation. Proteins. 2010;78:1163-74 pubmed publisher
    ..In addition to providing evidence to support a rotational activation mechanism, the simulations have enabled the nature of the interaction interfaces in both the cytokine-bound and unliganded hGHR states to be analyzed in detail. ..
  39. Christophidis L, Gorba T, Gustavsson M, Williams C, Werther G, Russo V, et al. Growth hormone receptor immunoreactivity is increased in the subventricular zone of juvenile rat brain after focal ischemia: a potential role for growth hormone in injury-induced neurogenesis. Growth Horm IGF Res. 2009;19:497-506 pubmed publisher
    ..These results indicate a novel role for GH and its receptor in injury-induced neurogenesis, and suggest that GH treatment may potentiate endogenous neuro-restorative processes after brain injury. ..
  40. Sasaki T, Maier B, Bartke A, Scrable H. Progressive loss of SIRT1 with cell cycle withdrawal. Aging Cell. 2006;5:413-22 pubmed
    ..Thus, as mitotic activity ceases in mouse and human cells in the normal environment of the animal or in the culture dish, there is a concomitant decline in the level of SIRT1. ..
  41. Nygren A, Sunnegardh J, Albertsson Wikland K, Berggren H, Isgaard J. Relative cardiac expression of growth hormone receptor and insulin-like growth factor-I mRNA in congenital heart disease. J Endocrinol Invest. 2008;31:196-200 pubmed
    ..50, p=0.04). This is the first study displaying cardiac expression of IGF-I mRNA and GH-R mRNA in children with congenital heart disease, although further studies are needed to define a role for GH in the treatment of these patients. ..
  42. Wu G, Zheng J, Yang N. [Expression profiling of GH, GHR, and IGF-1 genes in sex-linked dwarf chickens]. Yi Chuan. 2007;29:989-94 pubmed
    ..This transcript could be translated into a protein that does not retain its normal function, which would ac-count for the absence of GH-binding activity in liver membranes of the dwarf chickens. ..
  43. Gonzalez L, Curto L, Miquet J, Bartke A, Turyn D, Sotelo A. Differential regulation of membrane associated-growth hormone binding protein (MA-GHBP) and growth hormone receptor (GHR) expression by growth hormone (GH) in mouse liver. Growth Horm IGF Res. 2007;17:104-12 pubmed
    ..This attempt to attenuate the effects of supraphysiological concentrations of GH may be critical to reduce or prevent their plausible damaging effects on the organism. ..
  44. Bollerslev J, Fougner S, Berg J. New directions in pharmacological treatment of acromegaly. Expert Opin Investig Drugs. 2009;18:13-22 pubmed
    ..Treatment should be tailored for the individual case, also taking into account long-term effects, convenience for the patient and costs for society. ..
  45. Dehari R, Nakamura Y, Okamoto N, Nakayama H. Increased nuclear expression of growth hormone receptor in uterine cervical neoplasms of women under 40 years old. Tohoku J Exp Med. 2008;216:165-72 pubmed
    ..The GH-GHR signal may act at the nuclear level to promote the proliferation of uterine cervical neoplasms in young patients. We suggest the involvement of GHR in progression of uterine cervical carcinoma. ..
  46. Ni Y, Zhu Q, Zhou Z, Grossmann R, Chen J, Zhao R. Effect of dietary daidzein on egg production, shell quality, and gene expression of ER-alpha, GH-R, and IGF-IR in shell glands of laying hens. J Agric Food Chem. 2007;55:6997-7001 pubmed
    ..The results indicate that dietary daidzein improves egg laying performance and eggshell quality during the late (postpeak) laying stage of hens, which is associated with modulations in gene expression in the shell gland. ..
  47. Howell A. Fulvestrant ('Faslodex'): current and future role in breast cancer management. Crit Rev Oncol Hematol. 2006;57:265-73 pubmed
    ..Ongoing trials are investigating the efficacy of fulvestrant after failure on aromatase inhibitors and evaluating its use in combination with therapies that target growth factor receptor signaling pathways. ..
  48. Petkovic V, Godi M, Pandey A, Lochmatter D, Buchanan C, Dattani M, et al. Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action. J Clin Endocrinol Metab. 2010;95:731-9 pubmed publisher
  49. Bardeleben C, Moore R, Wayne R. A molecular phylogeny of the Canidae based on six nuclear loci. Mol Phylogenet Evol. 2005;37:815-31 pubmed
    ..The lack of resolution within the wolf-like canids may be due to their recent divergence and insufficient time for the accumulation of phylogenetically informative signal...
  50. Gómez Requeni P, Calduch Giner J, Vega Rubin de Celis S, Médale F, Kaushik S, Pérez Sánchez J. Regulation of the somatotropic axis by dietary factors in rainbow trout (Oncorhynchus mykiss). Br J Nutr. 2005;94:353-61 pubmed
  51. Li S, Hou G, Wang Y, Su X, Xue L. Influence of recombinant human growth hormone (rhGH) on proliferation of hepatocellular carcinoma cells with positive and negative growth hormone receptors in vitro. Tumori. 2010;96:282-8 pubmed
  52. Aguilar R, TALAMANTES F, Bustamante J, Munoz J, Treviño L, Martinez A, et al. MAP dendrimer elicits antibodies for detecting rat and mouse GH-binding proteins. J Pept Sci. 2009;15:78-88 pubmed publisher
    ..The antisera will facilitate studies aimed at improving our understanding of the biology of GH-BPs. ..
  53. Flint D, Binart N, Boumard S, Kopchick J, Kelly P. Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity. J Endocrinol. 2006;191:101-11 pubmed
    ..Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro. ..