دورية أكاديمية
Estradiol-driven metabolism in transwomen associates with reduced circulating extracellular vesicle microRNA-224/452.
| العنوان: | Estradiol-driven metabolism in transwomen associates with reduced circulating extracellular vesicle microRNA-224/452. |
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| المؤلفون: | Florijn BW; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Duijs JMGJ; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Klaver M; Department of Internal Medicine, Division of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands., Kuipers EN; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands., Kooijman S; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands., Prins J; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Zhang H; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Sips HCM; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands., Stam W; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Hanegraaf M; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Limpens RWAL; Department of Cell and Chemical Biology (Section Electron Microscopy), Leiden University Medical Center, Leiden, The Netherlands., Nieuwland R; Laboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry and Vesicle Observation Center, Amsterdam University Medical Center, Amsterdam, The Netherlands., van Rijn BB; Department of Obstetrics and Fetal Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands., Rabelink TJ; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., Rensen PCN; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands.; Department of Internal Medicine (Endocrinology), Leiden University Medical Center, Leiden, The Netherlands., den Heijer M; Department of Internal Medicine, Division of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands., Bijkerk R; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands., van Zonneveld AJ; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands. |
| المصدر: | European journal of endocrinology [Eur J Endocrinol] 2021 Aug 27; Vol. 185 (4), pp. 539-552. Date of Electronic Publication: 2021 Aug 27. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9423848 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-683X (Electronic) Linking ISSN: 08044643 NLM ISO Abbreviation: Eur J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: Oslo, Norway : Scandinavian University Press, c1994- |
| مواضيع طبية MeSH: | Transsexualism*/genetics , Transsexualism*/metabolism, Cell-Derived Microparticles/*genetics , Estradiol/*physiology , MicroRNAs/*genetics, Adipocytes/drug effects ; Adipocytes/physiology ; Adipogenesis/drug effects ; Adipogenesis/genetics ; Adult ; Animals ; Cell-Derived Microparticles/drug effects ; Cell-Derived Microparticles/metabolism ; Cohort Studies ; Down-Regulation/drug effects ; Down-Regulation/genetics ; Energy Metabolism/drug effects ; Energy Metabolism/genetics ; Estradiol/blood ; Estradiol/pharmacology ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Female ; Gene Expression Regulation/drug effects ; Homeostasis/drug effects ; Hormone Replacement Therapy ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; MicroRNAs/metabolism ; Middle Aged ; RNA Interference/drug effects ; Transgender Persons ; Young Adult |
| مستخلص: | Objective: 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. Methods: Following plasma miR-sequencing (seq) in a transwomen discovery (n = 20) and validation cohort (n = 30), we identified miR-224 and miR-452. Subsequent systemic silencing of these miRs in male C57Bl/6 J mice (n = 10) was followed by RNA-seq-based gene expression analysis of brown and white adipose tissue in conjunction with mechanistic studies in cultured adipocytes. Results: 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). Conclusion: This study identified an estradiol-drive post-transcriptional network that could potentially offer a mechanistic understanding of metabolism following gender-affirming estradiol therapy. |
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| المشرفين على المادة: | 0 (MIRN224 microRNA, human) 0 (MIRN452 microRNA, human) 0 (MicroRNAs) 4TI98Z838E (Estradiol) |
| تواريخ الأحداث: | Date Created: 20210803 Date Completed: 20210908 Latest Revision: 20220426 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8436186 |
| DOI: | 10.1530/EJE-21-0267 |
| PMID: | 34342596 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-683X |
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| DOI: | 10.1530/EJE-21-0267 |