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La Semaine Des Hopitaux : Organe Fonde...
Topics: Biological Phenomena; Growth; Growth Hormone; Human Growth Hormone; Physiological Phenomena
PubMed: 13246694
DOI: No ID Found -
Current Protein & Peptide Science Jun 2007Somatotropin, commonly known as growth hormone (GH) is a polypeptide chain containing about 190 amino acid residues, produced by the pituitary gland in mammals and is... (Review)
Review
Somatotropin, commonly known as growth hormone (GH) is a polypeptide chain containing about 190 amino acid residues, produced by the pituitary gland in mammals and is responsible for a number of anabolic processes. It has two disulphide bridges, with 4 alpha helices arranged in anti-parallel distinctive manner. GH molecule binds with two receptor molecules to exhibit its full biological activity. In this review, the information regarding characterization, structure and function is updated. A number of human growth hormone variants (naturally occurring and produced by recombinant DNA- technology) are visualised, and structure related functions are revealed. 1) The di-sulphide bridges are not essential for the biological activity of the molecule. The two chain variants of GH are able to show full biological activity. 2) The different domains of GH could be related to its functions 3) N-terminus of the molecule is involved in the galactopoietic activity of the molecule. 4) A single amino acid residue at a particular position could determine the magnitude of hormone receptor binding. 5) Role of Trp 86 is critical in packing of the apha helices bundles of the molecule. 6) Hydrophobic cores are essential for the stability of GH molecule 7) Salt bridges and hydrogen bonds are also important for the binding of the molecule with its receptors. 8) GH molecule has two binding sites for receptor molecules, Site I and Site II which are sterically coupled. The placental growth hormone has also been discussed and compared with the pituitary derived GH for its structure and function.
Topics: Animals; Binding Sites; Circular Dichroism; Disulfides; Genetic Variation; Growth Hormone; Human Growth Hormone; Humans; Models, Molecular; Protein Conformation; Sequence Deletion
PubMed: 17584122
DOI: 10.2174/138920307780831820 -
Journal of Neuroendocrinology Nov 2020
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Mice; Prolactin
PubMed: 33128814
DOI: 10.1111/jne.12909 -
Current Opinion in Investigational... Apr 2004Pfizer (formerly Pharmacia), in collaboration with its wholly owned subsidiary Sensus, has developed and launched pegvisomant, a pegylated, genetically modified human... (Review)
Review
Pfizer (formerly Pharmacia), in collaboration with its wholly owned subsidiary Sensus, has developed and launched pegvisomant, a pegylated, genetically modified human growth hormone (hGH), for the treatment of acromegaly. Pegvisomant, in contrast to classical somatostatin analogs which lower hGH synthesis, exerts its anti-hGH action by preventing GH receptor activation. This drug is now available in the US and Europe for the treatment of acromegaly.
Topics: Acromegaly; Animals; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Human Growth Hormone; Humans; Injections, Subcutaneous; Receptors, Somatotropin; Structure-Activity Relationship
PubMed: 15134290
DOI: No ID Found -
Molecular and Cellular Endocrinology Dec 2020In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is... (Review)
Review
In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is a cytokine receptor superfamily member that signals by activating the non-receptor tyrosine kinase, JAK2, and members of the Src family kinases. Activation of the GHR engages STATs, PI3K, and ERK pathways, among others, and details of these now-classical pathways are presented. Modulating elements, including the SOCS proteins, phosphatases, and regulated GHR metalloproteolysis, are discussed. In addition, a novel physical and functional interaction of GHR with IGF-1R is summarized and discussed in terms of its mechanisms, consequences, and physiological and therapeutic implications.
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Receptors, Somatotropin; Signal Transduction
PubMed: 32835785
DOI: 10.1016/j.mce.2020.110999 -
The New England Journal of Medicine Apr 2000
Topics: Acromegaly; Autoantibodies; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Receptors, Somatotropin
PubMed: 10770989
DOI: 10.1056/NEJM200004203421611 -
Hormone Research 2007
Topics: Acromegaly; Chemical and Drug Induced Liver Injury; Human Growth Hormone; Humans; Population Surveillance; Receptors, Somatotropin; Registries
PubMed: 18174712
DOI: 10.1159/000110480 -
Hispalis Medica; Revista Sevillana de... May 1956
Topics: Growth Hormone; Human Growth Hormone
PubMed: 13345260
DOI: No ID Found -
Growth Hormone & IGF Research :... Aug 2009Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms. The sources of this heterogeneity reside at the level of the genome, mRNA... (Review)
Review
Human growth hormone (GH) is a heterogeneous protein hormone consisting of several isoforms. The sources of this heterogeneity reside at the level of the genome, mRNA splicing, post-translational modification and metabolism. The GH gene cluster on chromosome 17q contains 2 GH genes (GH1 or GH-N and GH2 or GH-V) in addition to 2(-3) genes encoding the related chorionic somatomammotropin. Alternative mRNA splicing of the GH1 transcript yields two products: 22K-GH (the principal pituitary GH form) and 20K-GH. Post-translationally modified GH forms include N(alpha)-acylated, deamidated and glycosylated monomeric GH forms, as well as both non-covalent and disulfide-linked oligomers up to at least pentameric GH. GH fragments generated in the course of peripheral metabolism may be measured in immunoassays for GH. The GH-N gene is expressed in the pituitary, the GH-V gene in the placenta. Secretion of pituitary GH forms is pulsatile under control from the hypothalamus, whereas secretion of placental GH-V is tonic and rises progressively in maternal blood during the 2nd and 3rd trimester. Pituitary GH forms are co-secreted during a secretory pulse; no isoform-specific stimuli have been identified. There are minor differences in somatogenic and metabolic bioactivity among the GH isoforms, depending on species and assay system used. Both 20K-GH and GH-V have poor lactogenic activity. Oligomeric GH forms have variably diminished bioactivity compared to monomeric forms. GH isoforms cross-react in most immunoassays, but assays specific for 22K-GH, 20K-GH and GH-V have been developed. The metabolic clearance of 20K-GH and GH oligomers is delayed compared to that of 22K-GH. The heterogeneous mixture of GH isoforms in blood is further complicated by the presence of two GH-binding proteins, which form complexes with GH; isoform proportions also vary depending on the lag time from a secretory pulse because of different half-lives. GH forms excreted in the urine reflect monomeric GH isoforms in blood, but constitute only a minute fraction of the GH production rate. The heterogeneity of GH is one important reason for the notorious disparity among assay results. It also presents an opportunity for distinguishing endogenous from exogenous GH.
Topics: Amino Acid Sequence; Biological Assay; Chromosome Mapping; Dimerization; Glycosylation; Growth Hormone; Human Growth Hormone; Humans; Molecular Sequence Data; Multigene Family; Pituitary Gland; Protein Isoforms; Protein Processing, Post-Translational; Protein Structure, Tertiary; RNA, Messenger
PubMed: 19467614
DOI: 10.1016/j.ghir.2009.04.011 -
Clinical Endocrinology Sep 2013Daily recombinant growth hormone (GH) restores normal growth and body composition in GH-deficient children and adults; however, daily injections are inconvenient and can... (Review)
Review
Daily recombinant growth hormone (GH) restores normal growth and body composition in GH-deficient children and adults; however, daily injections are inconvenient and can be distressing for some children. On top of this compliance is a problem in up to 75% of children. Developing long-acting GH formulations has proved challenging, and questions remain regarding safety and efficacy. In this review, we focus on the rationale for generating long-acting GH agonists and the technologies being developed to deliver prolonged exposure to GH.
Topics: Adult; Body Composition; Chemistry, Pharmaceutical; Child; Drug Design; Human Growth Hormone; Humans; Recombinant Fusion Proteins
PubMed: 23662913
DOI: 10.1111/cen.12240