{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T01:40:01Z","timestamp":1763430001957,"version":"3.45.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>FK506-binding-protein-51 (FKBP51) is a glucocorticoid-induced co-chaperone protein previously shown to bind glucocorticoid receptor (GR), inhibiting its transcriptional activity. We previously found increased FKBP51 levels in uterine leiomyoma vs paired myometrium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To test the hypothesis that elevated FKBP51 levels contribute to leiomyoma pathogenesis by altering GR signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>RNA-sequencing was performed in leiomyoma cell cultures transfected with scramble or FKBP5-siRNA for 48 hours, then treated with vehicle or dexamethasone (DEX) for 24 hours. Differentially expressed genes, including HSD11B1, CNN1, and LAMA2 were analyzed by quantitative polymerase chain reaction. Hydroxysteroid 11-\u03b2 dehydrogenase 1 (HSD11\u03b21) expression was analyzed in leiomyoma, leiomyoma-adjacent paired myometrium, myometrium from patients without leiomyoma, and human endometrial stromal cells by quantitative polymerase chain reaction and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>University research institution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Women with or without uterine leiomyoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures<\/jats:title>\n                    <jats:p>HSD11B1 mRNA and protein levels in leiomyoma, paired myometrium, and normal myometrium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HSD11\u03b21 expression was higher in paired myometrial and leiomyoma tissues vs normal myometrium (P &amp;lt; .02). DEX treatment increased HSD11B1 transcription in normal myometrial and human endometrial stromal cell cultures, but to a significantly greater extent in leiomyoma (P &amp;lt; .001). However, FKBP5-silencing blunted this DEX-induced HSD11B1 upregulation. DEX-treatment reduced LAMA2 and increased CNN1 levels (coding for extracellular matrix and smooth muscle proteins, respectively) in FKBP5-silenced vs scramble siRNA-transfected leiomyoma cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FKBP51 not only inhibits but can augment GR-mediated transcription. Importantly, FKBP51-GR interactions increase HSD11B1 levels in leiomyoma cells, generating a pathological FKBP51-GR-HSD11\u03b21 circle, altering transcription of downstream extracellular matrix and smooth muscle genes to induce a myofibroblast phenotype, thereby possibly contributing to leiomyoma pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf255","type":"journal-article","created":{"date-parts":[[2025,4,27]],"date-time":"2025-04-27T08:00:44Z","timestamp":1745740844000},"page":"3370-3379","source":"Crossref","is-referenced-by-count":1,"title":["Increased HSD11\u03b21 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2939-8883","authenticated-orcid":false,"given":"Carrie","family":"Malcom","sequence":"first","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlem","family":"Guzeloglu-Kayisli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burak","family":"Un","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"New","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Busra","family":"Cetinkaya-Un","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emad","family":"Mikhail","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Imudia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"},{"name":"Shady Grove Fertility Center of Tampa Bay , Wesley Chapel, FL 33544 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Lockwood","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umit","family":"Kayisli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine , Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"issue":"10","key":"2025111718531267100_dgaf255-B1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/1471-0528.14640","article-title":"Epidemiology of uterine fibroids: a systematic review","volume":"124","author":"Stewart","year":"2017","journal-title":"BJOG Int J Obstet Gynaecol"},{"issue":"4","key":"2025111718531267100_dgaf255-B2","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.fertnstert.2015.12.021","article-title":"Mifepristone inhibits extracellular matrix formation in uterine leiomyoma","volume":"105","author":"Patel","year":"2016","journal-title":"Fertil Steril"},{"issue":"6","key":"2025111718531267100_dgaf255-B3","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1210\/en.2009-1225","article-title":"Progesterone is essential for maintenance and growth of uterine leiomyoma","volume":"151","author":"Ishikawa","year":"2010","journal-title":"Endocrinology"},{"issue":"3","key":"2025111718531267100_dgaf255-B4","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s12672-012-0103-0","article-title":"Glucocorticoids regulate gene expression and repress cellular proliferation in human uterine leiomyoma cells","volume":"3","author":"Whirledge","year":"2012","journal-title":"Horm Cancer"},{"issue":"11","key":"2025111718531267100_dgaf255-B5","first-page":"CD008994","article-title":"Progestogens or progestogen-releasing intrauterine systems for uterine fibroids (other than preoperative medical therapy)","volume":"11","author":"Sangkomkamhang","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"issue":"2 Suppl","key":"2025111718531267100_dgaf255-B6","first-page":"73","article-title":"Development of relugolix combination therapy as a medical treatment option for women with uterine fibroids or endometriosis","volume":"4","author":"Arjona Ferreira","year":"2023","journal-title":"FS Rep"},{"issue":"9","key":"2025111718531267100_dgaf255-B7","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1016\/j.ajpath.2015.05.014","article-title":"Enhanced human decidual cell-expressed FKBP51 may promote labor-related functional progesterone withdrawal","volume":"185","author":"Schatz","year":"2015","journal-title":"Am J Pathol"},{"issue":"6","key":"2025111718531267100_dgaf255-B8","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1074\/jbc.M407498200","article-title":"FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells","volume":"280","author":"Wochnik","year":"2005","journal-title":"J Biol Chem"},{"issue":"11","key":"2025111718531267100_dgaf255-B9","doi-asserted-by":"crossref","first-page":"4107","DOI":"10.1210\/endo.141.11.7785","article-title":"Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding","volume":"141","author":"Denny","year":"2000","journal-title":"Endocrinology"},{"issue":"5","key":"2025111718531267100_dgaf255-B10","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1038\/s41380-022-01491-0","article-title":"Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity","volume":"27","author":"Budzi\u00f1ski","year":"2022","journal-title":"Mol Psychiatry"},{"issue":"10","key":"2025111718531267100_dgaf255-B11","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1038\/cdd.2016.44","article-title":"The activity of the glucocorticoid receptor is regulated by SUMO conjugation to FKBP51","volume":"23","author":"Antunica-Noguerol","year":"2016","journal-title":"Cell Death Differ"},{"issue":"10","key":"2025111718531267100_dgaf255-B12","doi-asserted-by":"crossref","first-page":"e0137855","DOI":"10.1371\/journal.pone.0137855","article-title":"Progestins upregulate FKBP51 expression in human endometrial stromal cells to induce functional progesterone and glucocorticoid withdrawal: implications for contraceptive- associated abnormal uterine bleeding","volume":"10","author":"Kayisli","year":"2015","journal-title":"PLoS One"},{"issue":"11","key":"2025111718531267100_dgaf255-B13","doi-asserted-by":"crossref","first-page":"e2010282118","DOI":"10.1073\/pnas.2010282118","article-title":"Decidual cell FKBP51-progesterone receptor binding mediates maternal stress-induced preterm birth","volume":"118","author":"Guzeloglu-Kayisli","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"2025111718531267100_dgaf255-B14","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s43032-022-00921-2","article-title":"FKBP51 contributes to uterine leiomyoma pathogenesis by inducing cell proliferation and extracellular matrix deposition","volume":"29","author":"New","year":"2022","journal-title":"Reprod Sci Thousand Oaks Calif"},{"issue":"6","key":"2025111718531267100_dgaf255-B15","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1210\/jc.2011-3350","article-title":"Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome","volume":"97","author":"Fleseriu","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2025111718531267100_dgaf255-B16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jsbmb.2017.07.030","article-title":"The cortisol-activating enzyme 11\u03b2-hydroxysteroid dehydrogenase type 1 in skeletal muscle in the pathogenesis of the metabolic syndrome","volume":"174","author":"Loerz","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"issue":"8","key":"2025111718531267100_dgaf255-B17","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1021\/acschembio.8b00454","article-title":"Targeting the FKBP51\/GR\/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD","volume":"13","author":"Sabbagh","year":"2018","journal-title":"ACS Chem Biol"},{"issue":"1","key":"2025111718531267100_dgaf255-B18","first-page":"92","article-title":"Dysregulated expression of GATA2 and GATA6 transcription factors in adenomyosis: implications for impaired endometrial receptivity","volume":"5","author":"Pavlovic","year":"2024","journal-title":"FS Sci"},{"issue":"2","key":"2025111718531267100_dgaf255-B19","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1210\/clinem\/dgaa866","article-title":"Catecholestradiol activation of adrenergic receptors induces endometrial cell survival via p38 MAPK signaling","volume":"106","author":"Sprague","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"doi-asserted-by":"crossref","unstructured":"Malcom C, Guzeloglu\u2013Kayisli O, Un B, et al \u00a0Data from: Increased HSD11\u03b21 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling. NCBI GEO data repository, accession number GSE292403. Deposited 21 April 2025. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE292403","key":"2025111718531267100_dgaf255-B20","DOI":"10.1210\/clinem\/dgaf255"},{"issue":"7","key":"2025111718531267100_dgaf255-B21","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.chom.2023.05.018","article-title":"SINE RNA of the imprinted miRNA clusters mediates constitutive type III interferon expression and antiviral protection in hemochorial placentas","volume":"31","author":"Wickramage","year":"2023","journal-title":"Cell Host Microbe"},{"key":"2025111718531267100_dgaf255-B22","doi-asserted-by":"crossref","first-page":"898088","DOI":"10.3389\/fcell.2022.898088","article-title":"Preeclampsia is associated with reduced ISG15 levels impairing extravillous trophoblast invasion","volume":"10","author":"Ozmen","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"44","key":"2025111718531267100_dgaf255-B23","doi-asserted-by":"crossref","first-page":"15603","DOI":"10.1073\/pnas.0407008101","article-title":"Chromatin immunoprecipitation (ChIP) scanning identifies primary glucocorticoid receptor target genes","volume":"101","author":"Wang","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025111718531267100_dgaf255-B24"},{"issue":"12","key":"2025111718531267100_dgaf255-B25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.tem.2011.08.001","article-title":"FKBP51 and FKBP52 in signaling and disease","volume":"22","author":"Storer","year":"2011","journal-title":"Trends Endocrinol Metab"},{"issue":"8","key":"2025111718531267100_dgaf255-B26","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.psyneuen.2012.11.008","article-title":"Gene and protein alterations of FKBP5 and glucocorticoid receptor in the amygdala of suicide victims","volume":"38","author":"P\u00e9rez-Ortiz","year":"2013","journal-title":"Psychoneuroendocrinology"},{"issue":"10","key":"2025111718531267100_dgaf255-B27","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1172\/JCI69003","article-title":"Accelerated neurodegeneration through chaperone-mediated oligomerization of tau","volume":"123","author":"Blair","year":"2013","journal-title":"J Clin Invest"},{"issue":"3","key":"2025111718531267100_dgaf255-B28","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrm.2016.152","article-title":"Glucocorticoid receptor control of transcription: precision and plasticity via allostery","volume":"18","author":"Weikum","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025111718531267100_dgaf255-B29","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.3389\/fimmu.2019.01545","article-title":"A general Introduction to glucocorticoid biology","volume":"10","author":"Timmermans","year":"2019","journal-title":"Front Immunol"},{"issue":"5","key":"2025111718531267100_dgaf255-B30","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1093\/emboj\/cdg108","article-title":"The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo","volume":"22","author":"Riggs","year":"2003","journal-title":"EMBO J"},{"issue":"3","key":"2025111718531267100_dgaf255-B31","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1210\/me.2005-0318","article-title":"MED14 and MED1 differentially regulate target-specific gene activation by the glucocorticoid receptor","volume":"20","author":"Chen","year":"2006","journal-title":"Mol Endocrinol Baltim Md"},{"issue":"2","key":"2025111718531267100_dgaf255-B32","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s43032-023-01297-7","article-title":"The mediator Complex subunit 12 (MED-12) gene and uterine fibroids: a systematic review","volume":"31","author":"Amendola","year":"2024","journal-title":"Reprod Sci (Thousand Oaks Calif)"},{"issue":"1","key":"2025111718531267100_dgaf255-B33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1056\/NEJMoa1302736","article-title":"Characterization of uterine leiomyomas by whole-genome sequencing","volume":"369","author":"Mehine","year":"2013","journal-title":"N Engl J Med"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf255\/63019129\/dgaf255.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3370\/63019129\/dgaf255.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3370\/63019129\/dgaf255.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T23:53:38Z","timestamp":1763423618000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/12\/3370\/8120898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,4,28]]},"published-print":{"date-parts":[[2025,11,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf255","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"type":"print","value":"0021-972X"},{"type":"electronic","value":"1945-7197"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,4,28]]}}}