{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:21:56Z","timestamp":1793992916634,"version":"4.8.0"},"reference-count":195,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Growth hormone (GH) is a multifunctional regulator in somatic growth, metabolism, and tissue repair. Its pulsatile secretion is regulated by hypothalamic GH-releasing hormone (GHRH) and somatostatin (SST), and feedback inhibition by insulin-like growth factor 1 (IGF-1). Dysregulation of GH underlies several clinical disorders, including GH deficiency (GHD), acromegaly, and gigantism. The emerging concept of proteoformics has fundamentally reshaped the traditional view of GH: although human GH is encoded by a single gene, it gives rise to multiple proteoforms (GHPs) with distinct biological activities. In-depth study on GHPs pattern benefits understanding its precise molecular mechanism, discovering new therapeutic targets\/drugs, and constructing GHPs-based biomarkers. Integration of proteoformics with multi-omics facilitates the construction of dynamic regulatory networks for GH signaling, thereby providing robust support for biomarker discovery and precision medicine strategies in GH-related diseases. Proteoform-based personalized therapy holds promise to advance current treatments such as somatostatin receptor ligands (SRLs), growth hormone receptor (GHR) antagonists, and long-acting GH formulations, with emerging therapies like antisense oligonucleotides and oral GHRH agonists showing preliminary promise. This review examines the potential role of proteoform-centered multi-omics in advancing personalized diagnosis and treatment, discusses challenges in clinical translation, and outlines a roadmap for integrating GH proteoformics into predictive, preventive, and personalized medicine (3PM).<\/jats:p>","DOI":"10.3389\/fendo.2026.1842422","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T08:29:09Z","timestamp":1787214549000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteoformics-driven new concept of human growth hormone in clinical endocrinology"],"prefix":"10.3389","volume":"17","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences","place":["Jinan, China"]},{"name":"Shandong 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