{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:58:39Z","timestamp":1790445519073,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,23]]},"group-title":"Cell Biology","reference-count":18,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["T34GM136492"],"award-info":[{"award-number":["T34GM136492"]}]},{"name":"National Institutes of Health","award":["R01GM081685"],"award-info":[{"award-number":["R01GM081685"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Uterine leiomyomas, commonly known as fibroids, are benign tumors of the female reproductive tract. They are the most common tumor of the female reproductive system and the leading cause of hysterectomy in the United States. Progesterone, estrogen, and their receptors are important drivers for the development and growth of leiomyomas. How estrogen drives leiomyoma growth remains unclear. We have previously shown that simvastatin can inhibit leiomyoma growth by modulating intracellular calcium. This suggests that calcium signaling is important for leiomyoma growth. We therefore hypothesized that estrogen may drive leiomyoma growth by stimulating calcium release through the membrane estrogen receptor GPR30 (also known as GPER). We found that estrogen dose-dependently induced calcium release in leiomyoma cells. The GPR30-specific agonist G-1 also induced calcium release, indicating that GPR30 mediates estrogen-mediated calcium release. The GPR30 antagonist G-15 blocked estrogen-induced calcium release and significantly reduced leiomyoma proliferation. Our results demonstrate that GPR30 is a major driver of estrogen-dependent growth in leiomyoma cells by modulating intracellular calcium. These findings may have high therapeutic relevance to leiomyomas and other estrogen-dependent tumors.<\/jats:p>","DOI":"10.64898\/2026.09.22.753480","type":"posted-content","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:50:13Z","timestamp":1790171413000},"source":"Crossref","is-referenced-by-count":0,"title":["Estrogen is Coupled to the Calcium Release Machinery in Human Leiomyoma Cells"],"prefix":"10.64898","author":[{"given":"Ariana","family":"Machado","sequence":"first","affiliation":[{"name":"College of Science and Mathematics, Rowan University, Glassboro, NJ, USA"},{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Kaur","sequence":"additional","affiliation":[{"name":"College of Science and Mathematics, Rowan University, Glassboro, NJ, USA"},{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Kan","sequence":"additional","affiliation":[{"name":"Rowan-Virtua School of Osteopathic Medicine, Stratford, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-132X","authenticated-orcid":false,"given":"Mostafa","family":"Borahay","sequence":"additional","affiliation":[{"name":"Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-6922","authenticated-orcid":false,"given":"Darren","family":"Boehning","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092610251264000_2026.09.22.753480v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-015-2792-0"},{"key":"2026092610251264000_2026.09.22.753480v1.2","first-page":"100","article-title":"Uterine Fibroids: Diagnosis and Treatment","volume":"95","year":"2017","journal-title":"Am Fam Physician"},{"key":"2026092610251264000_2026.09.22.753480v1.3","doi-asserted-by":"publisher","DOI":"10.1177\/1933719116678686"},{"key":"2026092610251264000_2026.09.22.753480v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2011.122"},{"key":"2026092610251264000_2026.09.22.753480v1.5","doi-asserted-by":"crossref","first-page":"894","DOI":"10.3109\/09513590.2015.1092022","article-title":"G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced, proliferation of leiomyoma cells","volume":"31","year":"2015","journal-title":"Gynecol Endocrinol"},{"key":"2026092610251264000_2026.09.22.753480v1.6","first-page":"2773","article-title":"A nongenomic mechanism for \u201cmetalloestrogenic\u201d","volume":"93","year":"2019","journal-title":"effects of cadmium in human uterine leiomyoma cells through G proteincoupled estrogen receptor. 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