{"doi":"10.1113/expphysiol.2008.042515","title":"Growth hormone excess and the development of growth hormone receptor antagonists","abstract":"<jats:p>In 1990, a single amino acid substitution in the growth hormone (GH) gene at position 119 was found to transform the consequent protein from an agonist to an antagonist at the growth hormone receptor (GHR). Further amino acid substitutions plus prolongation of the half‐life of the protein by pegylation resulted in the first clinically effective GHR antagonist, pegvisomant. Following extensive clinical trials, this medication has emerged as the most efficacious therapy for treatment‐resistant acromegaly. Subsequent advances in our understanding of GH–GHR interactions and downstream GH signalling pathways suggest that pegvisomant binds to preformed GHR dimers and prevents rotational changes within the receptor–GH complex necessary for intracellular signalling to occur. This article reviews the discovery of pegvisomant, from initial experimental data to successful licensing of the drug for treatment‐resistant acromegaly, and discusses its other potential therapeutic uses in diseases with abnormalities in the GH–IGF‐I axis.</jats:p>","journal":"Experimental Physiology","year":2008,"id":596118,"datarank":1.725578625401477,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":1.1799407014425192,"self_endowment_contribution":0.5456379239589579,"citer_contribution":1.1799407014425192,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":36,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1526629,"name":"P. 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Subsequent advances in our understanding of GH–GHR interactions and downstream GH signalling pathways suggest that pegvisomant binds to preformed GHR dimers and prevents rotational changes within the receptor–GH complex necessary for intracellular signalling to occur. This article reviews the discovery of pegvisomant, from initial experimental data to successful licensing of the drug for treatment‐resistant acromegaly, and discusses its other potential therapeutic uses in diseases with abnormalities in the GH–IGF‐I axis.</jats:p>","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18617577","pmcid":null,"openalex_id":"https://openalex.org/W1587986748","authors":[],"funders":[],"total_grants":0,"fwci":2.5617,"citation_percentile":0.89650892,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":4},{"year":2014,"count":1},{"year":2015,"count":4},{"year":2016,"count":6},{"year":2017,"count":2},{"year":2019,"count":1},{"year":2022,"count":1},{"year":2024,"count":1}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/expphysiol.2008.042515","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1113/expphysiol.2008.042515","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1113%2Fexpphysiol.2008.042515","host_type":"publisher"},{"url":"https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2008.042515","host_type":"publisher"},{"url":"https://doi.org/10.1113/expphysiol.2008.042515","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18617577","host_type":"repository"},{"url":"https://research.manchester.ac.uk/en/publications/8038d66f-579f-40bc-928c-bc1a932ec58e","host_type":"repository"}],"fields_of_study":["Growth Hormone and Insulin-like Growth Factors","Pituitary Gland Disorders and Treatments","Genetic Syndromes and Imprinting","Acromegaly","Animals","Antineoplastic Agents","Carrier Proteins","Hormone Antagonists","Human Growth Hormone","Humans","Hypoglycemic Agents","Models, Molecular","Mutation","Protein Binding","Protein Conformation","Protein Multimerization","Signal Transduction"],"mesh_terms":["Acromegaly","Animals","Antineoplastic Agents","Carrier Proteins","Hormone Antagonists","Humans","Hypoglycemic Agents","Models, Molecular","Mutation","Protein Binding","Protein Conformation","Signal Transduction","Human Growth Hormone","Protein Multimerization"],"keywords":["Growth hormone receptor","Pegvisomant","Acromegaly","Receptor","Endocrinology","Internal medicine","Agonist","Antagonist","Pharmacology","Growth hormone-binding protein","Hormone","Growth hormone","Chemistry","Medicine","Biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T00:22:52.372666Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}