{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:01:27Z","timestamp":1791252087006,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"9","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\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171109"],"award-info":[{"award-number":["32171109"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thyroid hormone (TH) plays a vital role in ovarian follicle development, and glucose-regulated protein 78 (GRP78) is involved in these processes, which is regulated by TH. However, the mechanisms are still unclear. To evaluate the possible mechanism of TH on the regulation of GRP78 expression, Cleavage Under Targets and Tagmentation (CUT &amp; Tag) sequencing, luciferase assays, and Electrophoretic Mobility Shift Assays (EMSA) were employed to delineate the binding sites of thyroid hormone receptor \u03b2 (TR\u03b2) on the GRP78 promoter and to confirm the interactions. Additionally, Co-Immunoprecipitation (Co-IP) and Immunofluorescence (IF) assays were used to investigate the interactions between TR\u03b2 and the coactivator peroxisome proliferator-activated receptor \u03b3 coactivator 1\u03b1 (PGC-1\u03b1) after triiodothyronine (T3) treatment with different concentrations. Our findings identified a thyroid hormone response element (TRE) on the GRP78 promoter and demonstrated that TR\u03b2 can activate GRP78 expression by interacting with PGC-1\u03b1. In order to simulate the condition of hyperthyroidism, granulosa cells (GCs) extracted from rats were treated by T3 with high concentrations, which decreased the expression of PGC-1\u03b1, resulting in decreased expressions of GRP78 and other ferroptosis-related markers such as glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11, xCT), thereby inducing ferroptosis in GCs. Taken together, the present study demonstrates that T3 induces cellular ferroptosis by binding TRE of the GRP78 promoter in ovarian GCs via TR\u03b2. As a switcher, PGC-1\u03b1 is also involved in these processes.<\/jats:p>","DOI":"10.3390\/ijms26094196","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"4196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of T3 in the Regulation of GRP78 on Granulosa Cells in Rat Ovaries"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7749-6545","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"first","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyuan","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5951-8705","authenticated-orcid":false,"given":"Shuaitian","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1220-5164","authenticated-orcid":false,"given":"Yanzhou","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2962-0839","authenticated-orcid":false,"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Science, Capital Normal University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1071\/RD17362","article-title":"Regulation by 3,5,3\u2032-tri-iodothyronine and FSH of cytochrome P450 family 19 (CYP19) expression in mouse granulosa cells","volume":"30","author":"Liu","year":"2018","journal-title":"Reprod. 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