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Current Sports Medicine Reports 2010Growth hormone (hGH) presents pleiotropic effects in many tissues encompassing a diverse range of physiological actions. Its complexity as a family of hormones with... (Review)
Review
Growth hormone (hGH) presents pleiotropic effects in many tissues encompassing a diverse range of physiological actions. Its complexity as a family of hormones with different isoforms and different somatotroph molecular functions continues to challenge the status quo of our understanding of its release, function, and signaling. Owing to the fact that the majority of the literature has viewed hGH from the perspective of the primary 22 kD monomer, further investigation is needed as to the influence and biological activity of other aggregate and splice variant isoforms that are released into circulation. Its role over the life span and with supplementation yields equivocal results with more study needed. Testing for the use of hGH has progressed, and the first positive test was recently documented. Understanding of pituitary function and physiology will remain complex until the use of a broader range of analytical techniques, including assays, becomes mainstream.
Topics: Athletic Performance; Doping in Sports; Exercise; Human Growth Hormone; Humans; Time Factors
PubMed: 20622543
DOI: 10.1249/JSR.0b013e3181e976df -
General and Comparative Endocrinology Mar 2018Although growth hormone (GH) is a multifunctional factor that coordinates various aspects of feeding, reproduction, osmoregulation, and immune system function, perhaps... (Review)
Review
Although growth hormone (GH) is a multifunctional factor that coordinates various aspects of feeding, reproduction, osmoregulation, and immune system function, perhaps two of its most studied actions are the regulation of growth and metabolism, particularly lipid metabolism. In this review, we describe the major growth-promoting and lipid metabolic actions of GH and then discuss how the GH system regulates these actions. Numerous intrinsic and extrinsic factors provide information about the metabolic status of the organism and influence the production of release of GH. The actions of GH are mediated by GH receptors (GHR), which are widely distributed among tissues. Teleosts possess multiple forms of GHRs that arose through the evolution of this group. Modulation of tissue responsiveness to GH is regulated by molecular and functional expression of GHRs, and in teleosts GHR subtypes, by various factors that reflect the metabolic and growth status of the organism, including nutritional state. The action of GH is propagated by the linkage of GHRs to several cellular effector systems, including JAK-STAT, ERK, PI3K-Akt, and PKC. The differential activation of these pathways, which is governed by nutrient status, underlies GH stimulation of growth or GH stimulation of lipolysis. Taken together, the multi-functional actions of GH are determined by the distribution and abundance of GHRs (and GHR subtypes in teleosts) as well as by the GHR-effector system linkages.
Topics: Anabolic Agents; Animals; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Lipid Metabolism; Lipolysis; Metabolism; Phosphatidylinositol 3-Kinases; Receptors, Somatotropin; Signal Transduction
PubMed: 28760716
DOI: 10.1016/j.ygcen.2017.07.028 -
Nature Reviews. Endocrinology Sep 2010Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly... (Review)
Review
Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors.
Topics: Animals; Hormone Antagonists; Human Growth Hormone; Humans; Janus Kinase 2; Models, Biological; Models, Molecular; Mutation; Phosphorylation; Receptors, Somatotropin
PubMed: 20664532
DOI: 10.1038/nrendo.2010.123 -
Journal of the ASEAN Federation of... 2023Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH...
Primary growth hormone (GH) resistance or growth hormone insensitivity syndrome, also called Laron syndrome, is a hereditary disease caused by mutations in the GH receptor or in the post-receptor signaling pathway. This disorder is characterized by postnatal growth failure resembling GH deficiency. Differentiating the two conditions is necessary. We present the cases of two siblings, a 16-year-old female and a 9-year-old male, born from a consanguineous union. Both had normal birth weights with subsequent severe short stature and delayed teeth eruption, with no features suggestive of any systemic illness. Serum insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) were both low. Suspecting GH deficiency, provocative testing with clonidine was done revealing peak growth hormone >40 ng/mL in both patients. In view of low IGF1 and IGFBP3 and high GH on stimulation, IGF1 generation test was done for both siblings, with values supporting the diagnosis of GH insensitivity or Laron syndrome.
Topics: Male; Female; Humans; Adolescent; Child; Laron Syndrome; Siblings; Growth Hormone; Human Growth Hormone; Receptors, Somatotropin
PubMed: 38045665
DOI: 10.15605/jafes.038.02.22 -
Endocrine Reviews Oct 2002An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This... (Review)
Review
An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.
Topics: Acromegaly; Animals; Clinical Trials as Topic; Drug Design; Human Growth Hormone; Humans; Models, Molecular; Molecular Structure; Receptors, Somatotropin; Structure-Activity Relationship
PubMed: 12372843
DOI: 10.1210/er.2001-0022 -
Molecular and Cellular Endocrinology Apr 2014The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery,... (Review)
Review
The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer.
Topics: Amino Acid Sequence; Animals; Growth Hormone; Hormone Antagonists; Human Growth Hormone; Insulin-Like Growth Factor I; Mice; Molecular Sequence Data; Neoplasms; Receptors, Somatotropin
PubMed: 24035867
DOI: 10.1016/j.mce.2013.09.004 -
Diabetes 1959
Topics: Growth Hormone; Human Growth Hormone; Humans
PubMed: 13652754
DOI: 10.2337/diab.8.3.232 -
Best Practice & Research. Clinical... Dec 2016Recombinant human growth hormone (rhGH) has been available since 1985. Before 1985 growth hormone (GH) was extracted from cadaveric pituitary glands, but this was... (Review)
Review
Recombinant human growth hormone (rhGH) has been available since 1985. Before 1985 growth hormone (GH) was extracted from cadaveric pituitary glands, but this was stopped in most countries that year, following the recognition that it could transmit Creutzfeldt-Jacob disease. The primary goal of rhGH treatment in GHD patients is to normalize height during childhood and adolescence and attain an adult height within the normal range and within the target height range (genetic potential). Genome-wide association studies have been used increasingly to study the genetic influence on height. There is a wide response to rhGH therapy, likely due to compliance issues, severity of GH deficiency and patient's sensitivity to rhGH. While some pediatric endocrinologists will use a fixed dose of rhGH, most will use an auxology-based dosing approach. This will involve starting at the lower end of the dose range and then titrating upwards based on the patient's response to therapy with measurement of IGF-1 concentrations to ensure that the patient is not over treated or undertreated. Although treatment of children with GHD with rhGH has generally been safe, careful follow-up by a pediatric endocrinologist in partnership with the pediatrician or primary care physician is recommended. The aim of this paper is to review the strategies and recommendations for treatment of GHD in children and patients in the transition to adult care.
Topics: Adolescent; Child; Dwarfism, Pituitary; Hormone Replacement Therapy; Human Growth Hormone; Humans
PubMed: 27974188
DOI: 10.1016/j.beem.2016.11.005 -
Trends in Endocrinology and Metabolism:... Oct 2002Idiopathic short stature (ISS) is a term used for children in whom the etiology of the short stature is undefined. Investigations of the growth hormone (GH)-insulin-like... (Review)
Review
Idiopathic short stature (ISS) is a term used for children in whom the etiology of the short stature is undefined. Investigations of the growth hormone (GH)-insulin-like growth factor I axis have revealed several molecular and endocrinological defects in ISS patients. Abnormalities of GH secretion and action, although not frequent, will help to categorize some children with ISS. Because most diagnostic methods remain crude, however, their modification might be necessary to identify more subtle and yet functionally significant abnormalities of this endocrine axis.
Topics: Body Height; Child; Growth Disorders; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mutation; Receptors, Somatotropin; Signal Transduction
PubMed: 12217488
DOI: 10.1016/s1043-2760(02)00631-8 -
Journal of Pediatric Endocrinology &... Jul 2001Although it is difficult to reach international agreement on the definition of growth hormone deficiency (GHD) in children and adolescents, great efforts to do so have... (Review)
Review
Although it is difficult to reach international agreement on the definition of growth hormone deficiency (GHD) in children and adolescents, great efforts to do so have been made during the last two decades. A somewhat limited definition of GHD is: a combination of auxological, clinical, biochemical and metabolic abnormalities caused by lack or insufficiency of GH secretion that results in a decrease in the production of GH-dependent hormones and growth factors. Its aetiology is very complex. Therefore, specific studies must be performed during different periods of childhood (neonatal, prepubertal and pubertal periods). Auxological parameters, particularly growth velocity (GV), are still considered the best clinical measures for analysing human growth. The spectacular advances in our understanding of molecular biology during the past twenty years have allowed, and will continue to allow, a more and more precise diagnosis of the molecular anomalies of human growth. This will, in turn, allow changes caused by genetic lesions to be more efficiently distinguished from those due to nutritional, organic, tumoural, psychological or traumatic causes. Our knowledge of the molecular bases of undergrowth due to a deficiency in GH has developed as a result of the localisation and characterisation of human genes which code for proteins implicated in the hormonal regulation of growth. These genes include pituitary GH (GH1), pituitary transcription factor 1 (Pit-1), the prophet of Pit-1 (PROP-1), the pituitary transcription factor LHX3, the transcription factor HESX1 and the GH-releasing hormone receptor (GHRHr). In addition, magnetic resonance imaging is the best available imaging method for the evaluation of size and structure of the pituitary and the parasellar region.
Topics: Adolescent; Child; Female; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Male
PubMed: 11529396
DOI: 10.1515/jpem-2001-s213