{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:47:19Z","timestamp":1791870439337,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201023323505"],"award-info":[{"award-number":["RS\u20102025\u201023323505"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201002216753"],"award-info":[{"award-number":["RS\u20102025\u201002216753"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102026\u201025473498"],"award-info":[{"award-number":["RS\u20102026\u201025473498"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102026\u201025590558"],"award-info":[{"award-number":["RS\u20102026\u201025590558"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Chronic glucocorticoid (GC) therapy induces severe metabolic complications, notably secondary sarcopenia driven by excessive glucocorticoid receptor (GR)\u2010mediated catabolism. Although sex steroids protect skeletal muscle metabolism, the role of sex hormone\u2010binding globulin (SHBG), the primary determinant of sex steroid bioavailability, in modulating local endocrine crosstalk under GC stress remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the clinical correlation between serum SHBG and endocrine factors in a rheumatology cohort frequently exposed to GC. To establish causality and underlying mechanisms, male and female human SHBG\u2010transgenic (\n                      <jats:italic>hSHBG<\/jats:italic>\n                      \u2010Tg) mice, with or without gonadectomy, and C2C12 myoblasts were challenged with dexamethasone (DXM) to simulate GC\u2010induced muscle atrophy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In patients with high cumulative GC exposure (\u2265\u200910,000\u2009mg), circulating SHBG strongly inversely correlated with serum myostatin (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.7153,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0076). In mice,\n                      <jats:italic>hSHBG<\/jats:italic>\n                      \u2010Tg significantly rescued DXM\u2010induced loss of muscle mass (quadriceps, gastrocnemius, tibialis anterior) and grip strength in females; notably, this protection was entirely abolished by ovariectomy. Mechanistically,\n                      <jats:italic>hSHBG<\/jats:italic>\n                      \u2010Tg blunted GR Ser211 phosphorylation and downregulated the ubiquitin ligases\n                      <jats:italic>Fbxo32<\/jats:italic>\n                      and\n                      <jats:italic>Trim63<\/jats:italic>\n                      , while preserving estrogen receptor (ER) target genes (\n                      <jats:italic>Tff1<\/jats:italic>\n                      and\n                      <jats:italic>Pgr<\/jats:italic>\n                      ). In\u00a0vitro, estradiol antagonized DXM\u2010induced\n                      <jats:italic>Trim63<\/jats:italic>\n                      transcription via ER, and co\u2010treatment with SHBG sustained this anti\u2010catabolic effect by extending estradiol bioavailability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SHBG acts as a promoter of estrogen bioavailability that coordinates a protective endocrine crosstalk, counteracting GR\u2010driven catabolism in female skeletal muscle. These findings identify SHBG as a key metabolic determinant and a promising therapeutic target to prevent corticosteroid\u2010induced muscle wasting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70332","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:20:14Z","timestamp":1791868814000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex Hormone\u2010Binding Globulin Limits Glucocorticoid\u2010Induced Muscle Wasting by Preserving Estrogen\u2010Dependent Repression of Catabolic Signaling"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8309-3334","authenticated-orcid":false,"given":"Junyong","family":"Park","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine Dong\u2010A University College of Medicine  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah\u2010Young","family":"Song","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae\u2010Rahn","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Physiology Dong\u2010A University College of Medicine  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-8841","authenticated-orcid":false,"given":"Eui\u2010Ju","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-9854","authenticated-orcid":false,"given":"Sang R.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology Dong\u2010A University College of Medicine  Busan Republic of Korea"},{"name":"Department of Translational Biomedical Sciences Graduate School of Dong\u2010A University  Busan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging\u2010Related Loss of Muscle Mass and Function","volume":"99","author":"Larsson L.","year":"2019","journal-title":"Physiological Reviews"},{"issue":"1","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12891-020-03236-y","article-title":"Association Between Sarcopenia and Levels of Growth Hormone and Insulin\u2010Like Growth Factor\u20101 in the Elderly","volume":"21","author":"Bian A.","year":"2020","journal-title":"BMC Musculoskeletal Disorders"},{"issue":"1","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12020-012-9751-7","article-title":"Atrogin\u20101, MuRF\u20101, and Sarcopenia","volume":"43","author":"Gumucio J. 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Cell Physiology"},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2023.1156583","article-title":"From Mitochondria to Sarcopenia: Role of 17beta\u2010Estradiol and Testosterone","volume":"14","author":"Tian X.","year":"2023","journal-title":"Frontiers in Endocrinology"},{"issue":"18","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"5181","DOI":"10.1113\/JP286803","article-title":"Bioavailable Testosterone and Androgen Receptor Activation, but Not Total Testosterone, Are Associated With Muscle Mass and Strength in Females","volume":"603","author":"Alexander S. 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Cell Physiology"},{"issue":"8","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1093\/carcin\/bgz107","article-title":"Sex Hormone\u2010Binding Globulin Suppresses NAFLD\u2010Triggered Hepatocarcinogenesis After Menopause","volume":"40","author":"Lee S. R.","year":"2019","journal-title":"Carcinogenesis"},{"issue":"3","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.gendis.2021.10.003","article-title":"Sex Hormone\u2010Binding Globulin Impedes Hepatocellular Carcinoma Growth via MERTK Regulation","volume":"9","author":"Lee S. 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