{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:32:53Z","timestamp":1791844373100,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Sex steroid hormones like estrogens have a key role in the regulation of energy homeostasis and metabolism. In transwomen, gender-affirming hormone therapy like estradiol (in combination with antiandrogenic compounds) could affect metabolism as well. Given that the underlying pathophysiological mechanisms are not fully understood, this study assessed circulating estradiol-driven microRNAs (miRs) in transwomen and their regulation of genes involved in metabolism in mice.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Following plasma miR-sequencing (seq) in a transwomen discovery (<jats:italic>n<\/jats:italic>\u2009=\u200920) and validation cohort (<jats:italic>n<\/jats:italic>\u2009=\u200930), we identified miR-224 and miR-452. Subsequent systemic silencing of these miRs in male C57Bl\/6 J mice (<jats:italic>n<\/jats:italic>\u2009=\u200910) was followed by RNA-seq-based gene expression analysis of brown and white adipose tissue in conjunction with mechanistic studies in cultured adipocytes.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Estradiol in transwomen lowered plasma miR-224 and -452 carried in extracellular vesicles (EVs) while their systemic silencing in mice and cultured adipocytes increased lipogenesis (white adipose) but reduced glucose uptake and mitochondrial respiration (brown adipose). In white and brown adipose tissue, differentially expressed (miR target) genes are associated with lipogenesis (white adipose) and mitochondrial respiration and glucose uptake (brown adipose).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This study identified an estradiol-drive post-transcriptional network that could potentially offer a mechanistic understanding of metabolism following gender-affirming estradiol therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0267","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T12:59:19Z","timestamp":1627995559000},"page":"539-552","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":6,"title":["Estradiol-driven metabolism in transwomen associates with reduced circulating extracellular vesicle microRNA-224\/452"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9498-049X","authenticated-orcid":true,"given":"Barend W","family":"Florijn","sequence":"first","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques M G J","family":"Duijs","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maartje","family":"Klaver","sequence":"additional","affiliation":[{"name":"3Department of Internal Medicine, Division of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline N","family":"Kuipers","sequence":"additional","affiliation":[{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"4Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sander","family":"Kooijman","sequence":"additional","affiliation":[{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"4Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurrien","family":"Prins","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetty C M","family":"Sips","sequence":"additional","affiliation":[{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"4Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Stam","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"Hanegraaf","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald W A L","family":"Limpens","sequence":"additional","affiliation":[{"name":"5Department of Cell and Chemical Biology (Section Electron Microscopy), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rienk","family":"Nieuwland","sequence":"additional","affiliation":[{"name":"6Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry and Vesicle Observation Center, Amsterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas B","family":"van Rijn","sequence":"additional","affiliation":[{"name":"7Department of Obstetrics and Fetal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton J","family":"Rabelink","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C N","family":"Rensen","sequence":"additional","affiliation":[{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"4Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"den Heijer","sequence":"additional","affiliation":[{"name":"3Department of Internal Medicine, Division of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Bijkerk","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton Jan","family":"van Zonneveld","sequence":"additional","affiliation":[{"name":"1Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands"},{"name":"2Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/4\/EJE-21-0267.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/4\/EJE-21-0267.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:32Z","timestamp":1676391392000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/4\/539\/6654322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,1]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0267","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,1]]}}}