{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:41Z","timestamp":1792789361343,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 DK117633"],"award-info":[{"award-number":["R01 DK117633"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During the past 30 years, mouse models have been produced in which the expression of genes encoding steroid hormone receptors has been enhanced, partially compromised or eliminated. These mouse models have revealed many of the physiological processes regulated by androgens, estrogens and to a more limited extent glucocorticoids in the testis and male accessory organs. In this review, advances provided by mouse models that have facilitated a better understanding of the molecular regulation of testis and reproductive tract processes by steroid hormones are discussed.<\/jats:p>","DOI":"10.3390\/ijms24032748","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"2748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Functions of Steroid Hormones in the Male Reproductive Tract as Revealed by Mouse Models"],"prefix":"10.3390","volume":"24","author":[{"given":"William H.","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1095\/biolreprod.113.109132","article-title":"Androgen receptor (AR) physiological roles in male and female reproductive systems: Lessons learned from AR-knockout mice lacking AR in selective cells","volume":"89","author":"Chang","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/2271217a0","article-title":"X-linked gene for testicular feminization in the mouse","volume":"227","author":"Lyon","year":"1970","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13498","DOI":"10.1073\/pnas.212474399","article-title":"Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues","volume":"99","author":"Yeh","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1073\/pnas.0308114100","article-title":"A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis","volume":"101","author":"Swinnen","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2014.02.012","article-title":"The regulation of spermatogenesis by androgens","volume":"30","author":"Smith","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4161\/spmg.1.4.18740","article-title":"The development of an inducible androgen receptor knockout model in mouse to study the postmeiotic effects of androgens on germ cell development","volume":"1","author":"Willems","year":"2011","journal-title":"Spermatogenesis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1210\/en.2004-1630","article-title":"The role of androgens in Sertoli cell proliferation and functional maturation: Studies in mice with total or Sertoli cell-selective ablation of the androgen receptor","volume":"146","author":"Tan","year":"2005","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18975","DOI":"10.1073\/pnas.0608565103","article-title":"Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells","volume":"103","author":"Tsai","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1242\/dev.00957","article-title":"Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids","volume":"131","author":"Holdcraft","year":"2004","journal-title":"Development"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1210\/me.2012-1219","article-title":"Temporal role of Sertoli cell androgen receptor expression in spermatogenic development","volume":"27","author":"Hazra","year":"2013","journal-title":"Mol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1073\/pnas.0610814104","article-title":"Loss of androgen receptor binding to selective androgen response elements causes a reproductive phenotype in a knockin mouse model","volume":"104","author":"Schauwaers","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1210\/en.2012-2273","article-title":"Sertoli cell androgen receptor expression regulates temporal fetal and adult Leydig cell differentiation, function, and population size","volume":"154","author":"Hazra","year":"2013","journal-title":"Endocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sanz, E., Evanoff, R., Quintana, A., Evans, E., Miller, J.A., Ko, C., Amieux, P.S., Griswold, M.D., and McKnight, G.S. (2013). RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066179"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/me.2013-1391","article-title":"Genome-wide identification of AR-regulated genes translated in Sertoli cells in vivo using the RiboTag approach","volume":"28","author":"Verhoeven","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109557","DOI":"10.1016\/j.celrep.2021.109557","article-title":"Male fertility in mice requires classical and nonclassical androgen signaling","volume":"36","author":"Cooke","year":"2021","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1096\/fj.09-138347","article-title":"Androgen action via testicular peritubular myoid cells is essential for male fertility","volume":"23","author":"Welsh","year":"2009","journal-title":"FASEB J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17718","DOI":"10.1073\/pnas.0608556103","article-title":"Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells","volume":"103","author":"Zhang","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s12020-007-9015-0","article-title":"Infertility with defective spermatogenesis and steroidogenesis in male mice lacking androgen receptor in Leydig cells","volume":"32","author":"Xu","year":"2007","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1210\/en.2006-1223","article-title":"Disruption of prostate epithelial androgen receptor impedes prostate lobe-specific growth and function","volume":"148","author":"Simanainen","year":"2007","journal-title":"Endocrinology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12679","DOI":"10.1073\/pnas.0704940104","article-title":"Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor","volume":"104","author":"Wu","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/pros.21264","article-title":"Altered prostate epithelial development and IGF-1 signal in mice lacking the androgen receptor in stromal smooth muscle cells","volume":"71","author":"Yu","year":"2011","journal-title":"Prostate"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/pros.21445","article-title":"Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts","volume":"72","author":"Yu","year":"2012","journal-title":"Prostate"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1210\/me.2011-1189","article-title":"Suppressed prostate epithelial development with impaired branching morphogenesis in mice lacking stromal fibromuscular androgen receptor","volume":"26","author":"Lai","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1210\/en.2010-0768","article-title":"Targeted inactivation of the androgen receptor gene in murine proximal epididymis causes epithelial hypotrophy and obstructive azoospermia","volume":"152","author":"Krutskikh","year":"2011","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1210\/en.2010-0928","article-title":"Androgen receptor expression in the caput epididymal epithelium is essential for development of the initial segment and epididymal spermatozoa transit","volume":"152","author":"Welsh","year":"2011","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/37352","article-title":"A role for oestrogens in the male reproductive system","volume":"390","author":"Hess","year":"1997","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"E283","DOI":"10.1073\/pnas.1322057111","article-title":"Mutation of the palmitoylation site of estrogen receptor \u03b1 in vivo reveals tissue-specific roles for membrane versus nuclear actions","volume":"111","author":"Adlanmerini","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.devcel.2014.04.016","article-title":"Membrane-localized estrogen receptor \u03b1 is required for normal organ development and function","volume":"29","author":"Pedram","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Willems, A., Batlouni, S.R., Esnal, A., Swinnen, J.V., Saunders, P.T., Sharpe, R.M., Fran\u00e7a, L.R., De Gendt, K., and Verhoeven, G. (2010). Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014168"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1210\/en.2009-1333","article-title":"Direct action through the sertoli cells is essential for androgen stimulation of spermatogenesis","volume":"151","author":"Verhoeven","year":"2010","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1098\/rstb.2009.0117","article-title":"Androgens and spermatogenesis: Lessons from transgenic mouse models","volume":"365","author":"Verhoeven","year":"2010","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1210\/me.2006-0113","article-title":"Transcriptional profiling of androgen receptor (AR) mutants suggests instructive and permissive roles of AR signaling in germ cell development","volume":"21","author":"Eacker","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"763267","DOI":"10.3389\/fcell.2021.763267","article-title":"Single-Cell RNA Sequencing Defines the Regulation of Spermatogenesis by Sertoli-Cell Androgen Signaling","volume":"9","author":"Cao","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1091\/mbc.E20-05-0334","article-title":"Regulation of meiotic progression by Sertoli-cell androgen signaling","volume":"31","author":"Larose","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18722","DOI":"10.18632\/oncotarget.7916","article-title":"Androgen receptor in Sertoli cells regulates DNA double-strand break repair and chromosomal synapsis of spermatocytes partially through intercellular EGF-EGFR signaling","volume":"7","author":"Chen","year":"2016","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bolcun-Filas, E., Hall, E., Speed, R., Taggart, M., Grey, C., de Massy, B., Benavente, R., and Cooke, H.J. (2009). Mutation of the mouse Syce1 gene disrupts synapsis and suggests a link between synaptonemal complex structural components and DNA repair. PLoS Genet., 5.","DOI":"10.1371\/annotation\/50260271-aed9-4316-b09a-304591b0cba5"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1101\/gad.329705","article-title":"Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation","volume":"19","author":"Baarends","year":"2005","journal-title":"Genes Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.theriogenology.2007.09.029","article-title":"Disruption of pairing and synapsis of chromosomes causes stage-specific apoptosis of male meiotic cells","volume":"69","author":"Hamer","year":"2008","journal-title":"Theriogenology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Schramm, S., Fraune, J., Naumann, R., Hernandez-Hernandez, A., Hoog, C., Cooke, H.J., Alsheimer, M., and Benavente, R. (2011). A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet., 7.","DOI":"10.1371\/journal.pgen.1002088"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Walker, W.H., Easton, E., Moreci, R.S., and Toocheck, C. (2015). Anamthathmakula, and P. Jeyasuria. Restoration of spermatogenesis and male fertility using an androgen receptor transgene. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120783"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1365-2605.2011.01150.x","article-title":"Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells","volume":"35","author":"Welsh","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1002\/pros.20655","article-title":"Regulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expression","volume":"67","author":"Xu","year":"2007","journal-title":"Prostate"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1210\/en.2005-0300","article-title":"Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor","volume":"146","author":"Atanassova","year":"2005","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1242\/jcs.115.17.3491","article-title":"Failure of normal adult Leydig cell development in androgen-receptor-deficient mice","volume":"115","author":"Johnston","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"O\u2019Shaughnessy, P.J., Monteiro, A., and Abel, M. (2012). Testicular development in mice lacking receptors for follicle stimulating hormone and androgen. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035136"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"O\u2019Shaughnessy, P.J., Mitchell, R.T., Monteiro, A., O\u2019Hara, L., Cruickshanks, L., der Grinten, H.C., Brown, P., Abel, M., and Smith, L.B. (2019). Androgen receptor expression is required to ensure development of adult Leydig cells and to prevent development of steroidogenic cells with adrenal characteristics in the mouse testis. BMC Dev. Biol., 19.","DOI":"10.1186\/s12861-019-0189-5"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1210\/en.2011-0282","article-title":"Smooth muscle cell-specific knockout of androgen receptor: A new model for prostatic disease","volume":"152","author":"Welsh","year":"2011","journal-title":"Endocrinology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1210\/en.2007-1805","article-title":"Severe subfertility in mice with androgen receptor inactivation in sex accessory organs but not in testis","volume":"149","author":"Simanainen","year":"2008","journal-title":"Endocrinology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1210\/en.2009-1339","article-title":"Deletion of androgen receptor in the smooth muscle of the seminal vesicles impairs secretory function and alters its responsiveness to exogenous testosterone and estradiol","volume":"151","author":"Welsh","year":"2010","journal-title":"Endocrinology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1210\/en.2018-00529","article-title":"History of estrogen: Its purification, structure, synthesis, biologic actions, and clinical implications","volume":"160","author":"Santen","year":"2019","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/133209a0","article-title":"Mass excretion of oestrogenic hormone in the urine of the stallion","volume":"133","author":"Zondek","year":"1934","journal-title":"Nature"},{"key":"ref_52","first-page":"613","article-title":"Carcinoma mammae occurring in a male mouse under continued treatment with oestrin","volume":"24","author":"Burrows","year":"1935","journal-title":"Am. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/physrev.00018.2016","article-title":"Estrogens in male physiology","volume":"97","author":"Cooke","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3322\/canjclin.22.4.232","article-title":"Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate","volume":"22","author":"Huggins","year":"1972","journal-title":"CA Cancer. J. Clin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1056\/NEJM197104222841604","article-title":"Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women","volume":"284","author":"Herbst","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11162","DOI":"10.1073\/pnas.90.23.11162","article-title":"Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene","volume":"90","author":"Lubahn","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/biolre\/ioy043","article-title":"Estrogen in the male: A historical perspective","volume":"99","author":"Hess","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1385\/ENDO:12:3:207","article-title":"Normal development of thymus in male and female mice requires estrogen\/estrogen receptor-\u03b1 signaling pathway","volume":"12","author":"Yellayi","year":"2000","journal-title":"Endocrine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12729","DOI":"10.1073\/pnas.97.23.12729","article-title":"Increased adipose tissue in male and female estrogen receptor-\u03b1 knockout mice","volume":"97","author":"Heine","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1210\/endrev\/bnab041","article-title":"Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease","volume":"43","author":"Lange","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1210\/en.2016-1085","article-title":"Membrane-localized estrogen receptor 1 is required for normal male reproductive development and function in mice","volume":"157","author":"Nanjappa","year":"2016","journal-title":"Endocrinology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/acel.12170","article-title":"Acarbose, 17-\u03b1-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males","volume":"13","author":"Harrison","year":"2014","journal-title":"Aging Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/acel.12496","article-title":"Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an \u03b1-glucosidase inhibitor or a Nrf2-inducer","volume":"15","author":"Strong","year":"2016","journal-title":"Aging Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e13328","DOI":"10.1111\/acel.13328","article-title":"17-\u03b1-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex","volume":"20","author":"Harrison","year":"2021","journal-title":"Aging Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4252","DOI":"10.1210\/endo.139.10.6216","article-title":"Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor \u03b2","volume":"139","author":"Kuiper","year":"1998","journal-title":"Endocrinology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0022-4731(82)90184-4","article-title":"Effects of estradiol-17\u03b1 on nuclear occupancy of the estrogen receptor, stimulation of nuclear type II sites and uterine growth","volume":"16","author":"Clark","year":"1982","journal-title":"J. Steroid Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/j.exger.2004.05.006","article-title":"Estrogen and the brain: Beyond ER-\u03b1 and ER-\u03b2","volume":"39","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1210\/en.2004-1616","article-title":"17\u03b1-estradiol: A brain-active estrogen?","volume":"146","author":"Tinnikov","year":"2005","journal-title":"Endocrinology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e59616","DOI":"10.7554\/eLife.59616","article-title":"Health benefits attributed to 17\u03b1-estradiol, a lifespan-extending compound, are mediated through estrogen receptor \u03b1","volume":"9","author":"Mann","year":"2020","journal-title":"eLife"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:20:46Z","timestamp":1760120446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,1]]},"references-count":69,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032748"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032748","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,1]]}}}