{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T03:38:40Z","timestamp":1763091520741,"version":"3.41.2"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>To investigate the impact of growth hormone (GH) on branched\u2010chain amino acids (BCAAs) catabolism in males with hypopituitarism, we measured the concentration of amino acids in 133 males with hypopituitarism and 90 age\u2010matched healthy controls using untargeted metabolome. A rat model of hypopituitarism was established through hypophysectomy, followed by recombinant human GH (rhGH) intervention. Targeted metabolomics and label\u2010free quantitative phosphoproteomics were utilised to assess amino acid levels in rats and explore the mechanisms of GH's effect on BCAA catabolism. Hypopituitarism exhibited elevated concentrations of BCAAs, which correlated positively with triglyceride, fasting insulin and HOMA\u2010IR. The BCAAs were significantly elevated following hypophysectomy and were substantially reduced upon rhGH intervention. Phosphorylation proteomics analysis in liver tissues revealed that differentially expressed phosphoproteins (DEPPs) after GH treatment were predominantly involved in \u2018RNA metabolic process\u2019, \u2018Diseases of signal transduction by growth factor receptors\u2019 and \u2018BCAAs degradation\u2019. Notably, 12 proteins in the BCAA degradation pathway showed altered phosphorylation without whole protein changes. Importantly, the expression or phosphorylation modification of BCKDH, BCATs and MuRF1 were restored through rhGH intervention. Hypopituitarism exhibits elevated levels of circulating BCAAs. The increased circulating BCAAs in hypopituitarism may result from enhanced MuRF1\u2010mediated muscle proteolysis, which greatly exceeds the BCAA degradation capacity. This study provides valuable insights into the effects of GH on BCAA catabolism at the scale of the proteomics level.<\/jats:p>","DOI":"10.1111\/jcmm.70451","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:50:16Z","timestamp":1741726216000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Growth Hormone on Branched\u2010Chain Amino Acids Catabolism in Males With Hypopituitarism"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-2426","authenticated-orcid":false,"given":"Yuwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiqiu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pathology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enfei","family":"Xiang","sequence":"additional","affiliation":[{"name":"Clinical Research Center Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peizhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research Center Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0059-393X","authenticated-orcid":false,"given":"Xuqian","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1016\/S0140-6736(16)30053-8"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1159\/000485997"},{"issue":"2","key":"e_1_2_9_4_1","first-page":"CR75","article-title":"Risk Factors of Cardiovascular Disease in GH\u2010Deficient Adults With Hypopituitarism: A Preliminary Report","volume":"12","author":"Bohdanowicz\u2010Pawlak A.","year":"2006","journal-title":"Medical Science Monitor"},{"doi-asserted-by":"publisher","key":"e_1_2_9_5_1","DOI":"10.1530\/JME-13-0208"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1210\/er.2004-0022"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1210\/jc.2002-021943"},{"doi-asserted-by":"publisher","key":"e_1_2_9_8_1","DOI":"10.1210\/jcem.85.4.6541"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1126\/science.1065874"},{"issue":"2","key":"e_1_2_9_10_1","first-page":"44","article-title":"Protein Metabolism in Growth Hormone Deficiency, and Effects of Growth Hormone Replacement Therapy","volume":"128","author":"Russell\u2010Jones D. 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