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La Semana Medica Nov 1963
Topics: Biology; Blood; Growth Hormone; Human Growth Hormone; Pharmacology
PubMed: 14108876
DOI: No ID Found -
Endocrine-related Cancer Sep 2023Decades of published research support a role for growth hormone (GH) in cancer. Accordingly, there is increasing interest in targeting GH in oncology, with GH...
Decades of published research support a role for growth hormone (GH) in cancer. Accordingly, there is increasing interest in targeting GH in oncology, with GH antagonists exhibiting efficacy in xenograft studies as single agents and in combination with anticancer therapy or radiation. Here we discuss challenges associated with using growth hormone receptor (GHR) antagonists in preclinical models and considerations for translation, such as the identification of predictive biomarkers for selecting patients and for monitoring drug efficacy. Ongoing research will determine whether suppressing GH signalling pharmacologically will also reduce the risk of developing cancer. An increase in GH-targeted drugs in preclinical development will ultimately provide new tools to test anticancer efficacy of blocking the GH signalling pathway.
Topics: Humans; Growth Hormone; Receptors, Somatotropin; Human Growth Hormone; Neoplasms; Signal Transduction
PubMed: 37310137
DOI: 10.1530/ERC-23-0033 -
Hormone Research 2003The understanding of the mechanisms of growth hormone (GH) action has seen great accomplishments over the last two decades. These achievements include the cloning of a... (Review)
Review
The understanding of the mechanisms of growth hormone (GH) action has seen great accomplishments over the last two decades. These achievements include the cloning of a variety of GH and GH receptor (GHR) genes and cDNAs; solving of the three-dimensional structure of GH and the GH/GHR complex, and the discovery of GH antagonists. These GH antagonists have resulted in a new class of drugs with important clinical implications. Animal models in which the GH/insulin-like growth factor (IGF)-I axis has been perturbed also have resulted in many novel findings. We have now entered the era of genomics and proteomics. Genes and proteins that are up- or downregulated as a function of GH action (or lack thereof) will add to the repertoire of knowledge that will lead to a better understanding of the molecular basis of GH action.
Topics: Animals; Genomics; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Models, Molecular; Proteomics; Receptors, Somatotropin
PubMed: 14671406
DOI: 10.1159/000074510 -
European Journal of Endocrinology Apr 2003Using a structure-function approach to the understanding of the molecular topology of the GH molecule, we discovered that glycine in the third alpha-helix of GH (G119 of... (Review)
Review
Using a structure-function approach to the understanding of the molecular topology of the GH molecule, we discovered that glycine in the third alpha-helix of GH (G119 of bovine GH and G120 of human GH) was an important amino acid required for GH action. Substitution of this glycine residue with a variety of amino acids results in molecules that lack growth-promoting activity. More importantly, these molecules inhibit the actions of GH both in vitro and in vivo. These results, obtained more than a decade ago, were the basis for the discovery of GH antagonists. Since that time, efforts have been focused on establishing the mechanism by which these antagonists inhibit GH action. In this regard, in vivo expression of GH-antagonist genes in transgenic mice results in dwarf animals. The animals are fertile and possess no abnormal 'phenotypes'. Dwarf mice have also been created by disrupting or 'knocking out' the GH receptor gene. Together, these results have laid the foundation for the clinical use of GH antagonists when endogenous GH levels are increased or when GH is known to be a factor in the progression of the disorder.
Topics: Animals; Human Growth Hormone; Humans; Models, Molecular; Receptors, Somatotropin; Structure-Activity Relationship
PubMed: 12670297
DOI: 10.1530/eje.0.148s021 -
Growth Hormone & IGF Research :... Jun 2001Established modalities of therapy for acromegaly (surgical adenomectomy, external beam pituitary irradiation, oral dopamine agonists, and injectable somatostatin... (Review)
Review
Established modalities of therapy for acromegaly (surgical adenomectomy, external beam pituitary irradiation, oral dopamine agonists, and injectable somatostatin analogues) have as their common goal the lowering of circulating growth hormone (GH) levels, with a consequent reduction in serum insulin-like growth factor I (IGF-I). Pegvisomant is a GH receptor antagonist that inhibits GH receptor dimerization and has a powerful ability to lower serum IGF-I levels in patients with active acromegaly. Currently available data suggest that pegvisomant is an effective treatment for acromegaly that is safe, well tolerated, and not associated with expansion of residual pituitary tumour over the time period studied.
Topics: Acromegaly; Biomarkers; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Pituitary Neoplasms; Predictive Value of Tests; Receptors, Somatotropin
PubMed: 11527081
DOI: 10.1016/s1096-6374(01)80018-6 -
International Journal of Molecular... Sep 2022Growth hormone (GH) has been used as a co-gonadotrophin in assisted reproduction, particularly in poor ovarian responders. The application of GH has been alleged to... (Review)
Review
Growth hormone (GH) has been used as a co-gonadotrophin in assisted reproduction, particularly in poor ovarian responders. The application of GH has been alleged to activate primordial follicles and improve oocyte quality, embryo quality, and steroidogenesis. However, the effects of GH on the live birth rate among women is controversial. Additionally, although the basic biological mechanisms that lead to the above clinical differences have been investigated, they are not yet well understood. The actions of GH are mediated by GH receptors (GHRs) or insulin-like growth factors (IGFs). GH regulates the vital signal transduction pathways that are involved in primordial follicular activation, steroidogenesis, and oocyte maturation. However, the therapeutic windows and duration of GH administration during assisted reproductive technology require further investigation. The review aimed to clarify the role of GH in human fertility from a molecular and biological point of view to provide evidence for proper GH administration.
Topics: Female; Growth Hormone; Human Growth Hormone; Humans; Oogenesis; Receptors, Somatotropin; Somatomedins
PubMed: 36142677
DOI: 10.3390/ijms231810768 -
Therapeutic Drug Monitoring Feb 2009Human growth hormone (hGH) is a protein endogenously produced predominantly by the anterior pituitary gland. Native hGH and, especially, its recombinant analogue (rhGH),... (Review)
Review
Human growth hormone (hGH) is a protein endogenously produced predominantly by the anterior pituitary gland. Native hGH and, especially, its recombinant analogue (rhGH), used to treat patients with hormone deficiency, are supposed to be abused by athletes searching its anabolic and lipolytic effects. Hence, hGH use has been prohibited for a long time by the sport authorities, but until recently, hGH abuse could not be detected. Two approaches have been followed when trying to develop methods for GH abuse detection. The direct method identifies an abnormal ratio between GH isoforms--a result of hGH exogenous administration. The time window to find a cheating athlete by this approach is limited by the excretion time of the hormone. The indirect approach measures serum biomarkers directly affected by GH intake (eg, markers of released liver growth factors and of bone and collagen turnover). In this approach, the retrospective power extends further. Alternative possibilities for cheating related to hGH could be the administration of recombinant growth factors themselves, the administration of hGH metabolic precursors such as ghrelin-like GH secretagogues, or the genetic manipulation of muscle growth-related genes (gene doping). In parallel with the new types of abuse, which will surely emerge in the near future, the research and development for the improvement of the analytical detection of GH itself will continue.
Topics: Athletic Performance; Biomarkers; Doping in Sports; Gene Transfer Techniques; Ghrelin; Growth Hormone; Human Growth Hormone; Humans; Substance Abuse Detection
PubMed: 19155963
DOI: 10.1097/FTD.0b013e318194cc94 -
Bailliere's Best Practice & Research.... Mar 2000Doping with growth hormone (GH) has become an increasing problem in sports during the last 10 years. GH has a reputation of being fairly effective among GH users,... (Review)
Review
Doping with growth hormone (GH) has become an increasing problem in sports during the last 10 years. GH has a reputation of being fairly effective among GH users, although the effectiveness is not undisputed, and the few controlled studies that have been performed with supraphysiological GH doses to athletes have shown no significant positive effects of GH in the aspect of a doping agent. There is no method yet to discover GH doping, but current intensive research in this matter will hopefully produce a method in the years to come. This article describes the GH physiology, the clinical use of GH, the athlete's view, administration regimens and side effects.
Topics: Doping in Sports; Exercise; Human Growth Hormone; Humans; Substance Abuse Detection
PubMed: 10932811
DOI: 10.1053/beem.2000.0054 -
The Journal of Clinical Endocrinology... Apr 2004
Review
Topics: Acromegaly; Animals; Antineoplastic Agents; Growth Hormone; Human Growth Hormone; Humans; Kidney Diseases; Mammary Neoplasms, Animal; Molecular Structure; Receptors, Somatotropin; Retinal Diseases
PubMed: 15070905
DOI: 10.1210/jc.2002-022049 -
Endocrine Development 2012Advances in novel molecular biological diagnostic methods are changing the way of diagnosis and study of metabolic disorders like growth hormone deficiency. Faster... (Review)
Review
Advances in novel molecular biological diagnostic methods are changing the way of diagnosis and study of metabolic disorders like growth hormone deficiency. Faster sequencing and genotyping methods require strong bioinformatics tools to make sense of the vast amount of data generated by modern laboratories. Advances in genome sequencing and computational power to analyze the whole genome sequences will guide the diagnostics of future. In this chapter, an overview of some basic bioinformatics resources that are needed to study metabolic disorders are reviewed and some examples of bioinformatics analysis of human growth hormone gene, protein and structure are provided.
Topics: Amino Acid Sequence; Computational Biology; Databases, Genetic; Genomics; Human Growth Hormone; Humans; Models, Biological; Models, Molecular; Molecular Sequence Data; Protein Structure, Secondary; Software
PubMed: 23182822
DOI: 10.1159/000341755