{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:04:36Z","timestamp":1782320676721,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD103573"],"award-info":[{"award-number":["P50 HD103573"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glucocorticoids are primary stress hormones necessary for life that act on nearly every tissue in the body to maintain homeostasis. These hormones and their synthetic derivatives are widely used in the clinic to combat disease but are limited by serious adverse effects. The actions of glucocorticoids are mediated by the glucocorticoid receptor (GR). In addition to the classic full\u2010length receptor (GR\u2010A), seven highly conserved receptor isoforms with progressively shorter N\u2010terminal transactivation domains (NTD) (GR\u2010B, GR\u2010C1, GR\u2010C2, GR\u2010C3, GR\u2010D1, GR\u2010D2, GR\u2010D3) are produced from the single GR gene by alternative translation initiation. To investigate the physiological function of these isoforms, we developed knockin mice that express GR\u2010A but lack the GR NTD translational isoforms. Analyses of the hippocampal transcriptome from wild\u2010type and GR\u2010A knockin mice treated with dexamethasone (Dex) revealed three classes of Dex\u2010regulated genes: genes dependent on GR\u2010A alone, genes dependent on the GR NTD translational isoforms, and genes dependent on GR\u2010A only under conditions of GR NTD isoform deficiency. The genes dependent on the GR NTD isoforms were preferentially associated with circadian rhythm signaling, synaptic function, and cognition. Consistent with these gene enrichment results, the GR\u2010A knockin mice exhibited alterations in hypothalamic\u2013pituitary\u2013adrenal axis activity and fear\u2010motivated contextual learning. The GR NTD translational isoforms formed distinct molecular complexes with GR\u2010A and with each other, providing a mechanistic basis for their unique transcriptional signatures. These findings demonstrate that the GR NTD translational isoforms contribute to the actions of glucocorticoids in the brain by generating heterogeneity in glucocorticoid signaling.<\/jats:p>","DOI":"10.1096\/fj.202601316r","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:50:46Z","timestamp":1781103046000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucocorticoid Receptor Translational Isoforms Generate Unique Glucocorticoid Responses in the Mouse Brain"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7317-2223","authenticated-orcid":false,"given":"Robert H.","family":"Oakley","sequence":"first","affiliation":[{"name":"Molecular and Cellular Biology Laboratory NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sueyoshi","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Laboratory NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivapriya","family":"Ramamoorthy","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Laboratory NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoriya D.","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Goulding","sequence":"additional","affiliation":[{"name":"Comparative Medicine Branch NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Li","sequence":"additional","affiliation":[{"name":"Biostatistics and Computational Biology Branch NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manas K.","family":"Ray","sequence":"additional","affiliation":[{"name":"Gene Editing and Mouse Model Core NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheryl S.","family":"Moy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Carolina Institute for Developmental Disabilities University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Cidlowski","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Biology Laboratory NIEHS, NIH, DHHS  Research Triangle Park North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.09.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.21.1.55"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050541"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283939"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnae008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.03.025"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00253-07"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701153R"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.193"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.05.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-020-00413-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.160"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-12-84"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2010.28"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202101122"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2021.100369"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2025.108488"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.188581.114"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0418-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16100"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.7.0667"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.215"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2018.1470238"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/10253890.2020.1859475"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.09.002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-014-0483-7"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2012007500041"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1006\/nlme.2002.4080"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2651"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.06.020"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1006\/nlme.1996.3741"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.111.3.503"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.09.012"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13294"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/387497a0"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20010055"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.12.004"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11040683"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.07.012"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049458u"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0467"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2021.03.013"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202601316R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202601316R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202601316R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T16:23:44Z","timestamp":1782318224000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202601316R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,10]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2026,6,30]]}},"alternative-id":["10.1096\/fj.202601316R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202601316r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,10]]},"assertion":[{"value":"2026-03-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72040"}}