{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:24:25Z","timestamp":1790753065756,"version":"4.1.0"},"reference-count":60,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Nuclear receptor subfamily 4 group A member1 (NR4A1), an orphan nuclear receptor, is involved in the transcriptional regulation of thecal cell androgen biosynthesis and paracrine factor insulin-like 3 (INSL3) expression. Androgens are known to play an important regulatory role in ovarian follicle growth. Using a chronically androgenized rat model, a preantral follicle culture model and virus-mediated gene delivery, we examined the role and regulation of NR4A1 in the androgenic control of preantral follicular growth. In the present study, Ki67 staining was increased in preantral follicles on ovarian sections from 5\u03b1-dihydrotestosterone (DHT)-treated rats. Preantral follicles from DHT-treated rats cultured for 4 d exhibited increased growth and up-regulation of mRNA abundance of G1\/S-specific cyclin-D2 (Ccnd2) and FSH receptor (Fshr). Similarly, DHT (1 \u03bcm) increased preantral follicular growth and Ccnd2 and Fshr mRNA abundance in vitro. The NR4A1 expression was high in theca cells and was down-regulated by DHT in vivo and in vitro. Forced expression of NR4A1 augmented preantral follicular growth, androstenedione production, and Insl3 expression in vitro. Inhibiting the action of androgen (with androgen receptor antagonist flutamide) or INSL3 (with INSL3 receptor antagonist INSL3 B-chain) reduced NR4A1-induced preantral follicular growth. Furthermore, NR4A1 overexpression enhanced DHT-induced preantral follicular growth, a response attenuated by inhibiting INSL3. In conclusion, DHT promotes preantral follicular growth and attenuates thecal NR4A1 expression in vivo and in vitro. Our findings are consistent with the notion that NR4A1 serves as an important point of negative feedback to minimize the excessive preantral follicle growth in hyperandrogenism.<\/jats:p>","DOI":"10.1210\/me.2012-1200","type":"journal-article","created":{"date-parts":[[2012,10,2]],"date-time":"2012-10-02T03:22:44Z","timestamp":1349148164000},"page":"2004-2015","source":"Crossref","is-referenced-by-count":27,"title":["Orphan Nuclear Receptor NR4A1 Is a Negative Regulator of DHT-Induced Rat Preantral Follicular Growth"],"prefix":"10.1210","volume":"26","author":[{"given":"Kai","family":"Xue","sequence":"first","affiliation":[{"name":"State Key Laboratory in Reproductive Medicine (K.X., J.-Y.L.), Centre for Clinical Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China"},{"name":"Departments of Cellular and Molecular Medicine and Obstetrics and Gynecology (K.X., B.K.T.), University of Ottawa, Ottawa, Ontario, Canada K1H 8L6; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1Y 4E9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-yin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory in Reproductive Medicine (K.X., J.-Y.L.), Centre for Clinical Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Centre for Animal Reproduction Research (B.D.M.), University of Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada H3T 1C5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin K.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Departments of Cellular and Molecular Medicine and Obstetrics and Gynecology (K.X., B.K.T.), University of Ottawa, Ottawa, Ontario, Canada K1H 8L6; Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1Y 4E9"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613255797600_B1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0303-7207(01)00614-1","article-title":"Stage-dependent role of growth differentiation factor-9 in ovarian follicle development.","volume":"183","author":"Vitt","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613255797600_B2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.anireprosci.2004.05.017","article-title":"Oocyte-somatic cell interactions during follicle development in mammals.","volume":"82\u201383","author":"Gilchrist","year":"2004","journal-title":"Anim Reprod Sci"},{"key":"2020071613255797600_B3","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1210\/jcem-52-5-994","article-title":"Changes in enzyme activities related to steroidogenesis in human ovaries during the menstrual cycle.","volume":"52","author":"Sano","year":"1981","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613255797600_B4","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1095\/biolreprod62.2.370","article-title":"Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles.","volume":"62","author":"Vitt","year":"2000","journal-title":"Biol Reprod"},{"key":"2020071613255797600_B5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1677\/JME-07-0145","article-title":"Glucocorticoids antagonize cAMP-induced Star transcription in Leydig cells through the orphan nuclear receptor NR4A1.","volume":"41","author":"Martin","year":"2008","journal-title":"J Mol Endocrinol"},{"key":"2020071613255797600_B6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/00006254-198202000-00001","article-title":"Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called \u201chyperthecosis.\u201d","volume":"37","author":"Hughesdon","year":"1982","journal-title":"Obstet Gynecol Surv"},{"key":"2020071613255797600_B7","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.steroids.2003.07.009","article-title":"Involvement of multiple transcription factors in the regulation of steroidogenic acute regulatory protein gene expression.","volume":"68","author":"Manna","year":"2003","journal-title":"Steroids"},{"key":"2020071613255797600_B8","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1210\/en.2007-1265","article-title":"Positive regulation of steroidogenic acute regulatory protein gene expression through the interaction between Dlx and GATA-4 for testicular steroidogenesis.","volume":"149","author":"Nishida","year":"2008","journal-title":"Endocrinology"},{"key":"2020071613255797600_B9","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1677\/joe.0.174r013","article-title":"Liver receptor homologue-1 is expressed in human steroidogenic tissues and activates transcription of genes encoding steroidogenic enzymes.","volume":"174","author":"Sirianni","year":"2002","journal-title":"J Endocrinol"},{"key":"2020071613255797600_B10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0303-7207(01)00423-3","article-title":"Elements involved in the regulation of the StAR gene.","volume":"177","author":"Stocco","year":"2001","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613255797600_B11","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1101\/gad.9.7.769","article-title":"A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1.","volume":"9","author":"Perlmann","year":"1995","journal-title":"Genes Dev"},{"key":"2020071613255797600_B12","first-page":"1656","article-title":"Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1.","volume":"10","author":"Zetterstr\u00f6m","year":"1996","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B13","doi-asserted-by":"crossref","first-page":"7549","DOI":"10.1128\/MCB.19.11.7549","article-title":"Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation.","volume":"19","author":"Maira","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2020071613255797600_B14","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0092-8674(04)00162-X","article-title":"Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77\/TR3.","volume":"116","author":"Lin","year":"2004","journal-title":"Cell"},{"key":"2020071613255797600_B15","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1126\/science.276.5310.248","article-title":"Dopamine neuron agenesis in Nurr1-deficient mice.","volume":"276","author":"Zetterstr\u00f6m","year":"1997","journal-title":"Science"},{"key":"2020071613255797600_B16","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/nm1471","article-title":"NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism.","volume":"12","author":"Pei","year":"2006","journal-title":"Nat Med"},{"key":"2020071613255797600_B17","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1210\/me.2005-0331","article-title":"Regulation of macrophage inflammatory gene expression by the orphan nuclear receptor Nur77.","volume":"20","author":"Pei","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B18","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1161\/01.CIR.0000028811.03056.BF","article-title":"Protective function of transcription factor TR3 orphan receptor in atherogenesis: decreased lesion formation in carotid artery ligation model in TR3 transgenic mice.","volume":"106","author":"Arkenbout","year":"2002","journal-title":"Circulation"},{"key":"2020071613255797600_B19","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1210\/me.2008-0161","article-title":"Inhibition of adipocyte differentiation by Nur77, Nurr1, and Nor1.","volume":"22","author":"Chao","year":"2008","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B20","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1210\/en.2004-0859","article-title":"The human 3\u03b2-hydroxysteroid dehydrogenase\/\u03945-\u03944 isomerase type 2 promoter is a novel target for the immediate early orphan nuclear receptor Nur77 in steroidogenic cells.","volume":"146","author":"Martin","year":"2005","journal-title":"Endocrinology"},{"key":"2020071613255797600_B21","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1210\/mend.11.7.9940","article-title":"Multiple orphan nuclear receptors converge to regulate rat P450c17 gene transcription: novel mechanisms for orphan nuclear receptor action.","volume":"11","author":"Zhang","year":"1997","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B22","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1095\/biolreprod.105.044560","article-title":"The orphan nuclear receptor NR4A1 regulates insulin-like 3 gene transcription in Leydig cells.","volume":"74","author":"Robert","year":"2006","journal-title":"Biol Reprod"},{"key":"2020071613255797600_B23","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1530\/ror.0.0020133","article-title":"Biology of the relaxin-like factor (RLF).","volume":"2","author":"Ivell","year":"1997","journal-title":"Rev Reprod"},{"key":"2020071613255797600_B24","doi-asserted-by":"crossref","first-page":"13068","DOI":"10.1074\/jbc.M600472200","article-title":"Analogs of insulin-like peptide 3 (INSL3) B-chain are LGR8 antagonists in vitro and in vivo.","volume":"281","author":"Del Borgo","year":"2006","journal-title":"J Biol Chem"},{"key":"2020071613255797600_B25","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/1098-2795(200103)58:3<281::AID-MRD6>3.0.CO;2-0","article-title":"Increase in final stages of follicular atresia and premature decay of corpora lutea in Insl3-deficient mice.","volume":"58","author":"Spanel-Borowski","year":"2001","journal-title":"Mol Reprod Dev"},{"key":"2020071613255797600_B26","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1210\/en.2007-0168","article-title":"A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome.","volume":"148","author":"Manner\u00e5s","year":"2007","journal-title":"Endocrinology"},{"key":"2020071613255797600_B27","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1210\/me.2005-0357","article-title":"Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage.","volume":"20","author":"Orisaka","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B28","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1210\/en.2008-1536","article-title":"Growth differentiation factor 9 promotes rat preantral follicle growth by up-regulating follicular androgen biosynthesis.","volume":"150","author":"Orisaka","year":"2009","journal-title":"Endocrinology"},{"key":"2020071613255797600_B29","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1095\/biolreprod.102.007807","article-title":"Role and gonadotrophic regulation of X-linked inhibitor of apoptosis protein expression during rat ovarian follicular development in vitro.","volume":"68","author":"Wang","year":"2003","journal-title":"Biol Reprod"},{"key":"2020071613255797600_B30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.mce.2010.01.014","article-title":"The orphan nuclear receptor NR4A1 regulates transcription of key steroidogenic enzymes in ovarian theca cells.","volume":"319","author":"Li","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613255797600_B31","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1093\/oxfordjournals.humrep.a137614","article-title":"Immunohistochemical localization of androgen receptor in the human ovary throughout the menstrual cycle in relation to oestrogen and progesterone receptor expression.","volume":"7","author":"Horie","year":"1992","journal-title":"Hum Reprod"},{"key":"2020071613255797600_B32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0960-0760(94)90294-1","article-title":"Androgen receptor mRNA in the rat ovary and uterus.","volume":"49","author":"Hirai","year":"1994","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071613255797600_B33","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1677\/joe.0.1450535","article-title":"Developmental regulation of androgen receptor in rat ovary.","volume":"145","author":"Tetsuka","year":"1995","journal-title":"J Endocrinol"},{"key":"2020071613255797600_B34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/humrep\/12.1.107","article-title":"Location and developmental regulation of androgen receptor in primate ovary.","volume":"12","author":"Hillier","year":"1997","journal-title":"Hum Reprod"},{"key":"2020071613255797600_B35","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1210\/jcem.83.7.4917","article-title":"Androgen receptor gene expression in the primate ovary: cellular localization, regulation, and functional correlations.","volume":"83","author":"Weil","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613255797600_B36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/mrd.10060","article-title":"Androgen receptor and follicle-stimulating hormone receptor in the pig ovary during the follicular phase of the estrous cycle.","volume":"62","author":"C\u00e1rdenas","year":"2002","journal-title":"Mol Reprod Dev"},{"key":"2020071613255797600_B37","doi-asserted-by":"crossref","first-page":"11209","DOI":"10.1073\/pnas.0404372101","article-title":"Subfertility and defective folliculogenesis in female mice lacking androgen receptor.","volume":"101","author":"Hu","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613255797600_B38","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1095\/biolreprod27.4.903","article-title":"A model for the study of androgen effects on follicular atresia and ovulation.","volume":"27","author":"Bagnell","year":"1982","journal-title":"Biol Reprod"},{"key":"2020071613255797600_B39","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1210\/endo.133.5.8404672","article-title":"Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis.","volume":"133","author":"Billig","year":"1993","journal-title":"Endocrinology"},{"key":"2020071613255797600_B40","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1172\/JCI2081","article-title":"Androgens stimulate early stages of follicular growth in the primate ovary.","volume":"101","author":"Vendola","year":"1998","journal-title":"J Clin Invest"},{"key":"2020071613255797600_B41","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1530\/jrf.0.1130027","article-title":"Effect of androgens on the development of mouse follicles growing in vitro.","volume":"113","author":"Murray","year":"1998","journal-title":"J Reprod Fertil"},{"key":"2020071613255797600_B42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1530\/jrf.0.1130019","article-title":"Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro.","volume":"113","author":"Spears","year":"1998","journal-title":"J Reprod Fertil"},{"key":"2020071613255797600_B43","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1210\/endo.142.11.8482","article-title":"Effect of adrenal and ovarian androgens on type 4 follicles unresponsive to FSH in immature mice.","volume":"142","author":"Wang","year":"2001","journal-title":"Endocrinology"},{"key":"2020071613255797600_B44","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1210\/jcem.84.8.5929","article-title":"Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development.","volume":"84","author":"Weil","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613255797600_B45","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/384470a0","article-title":"Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.","volume":"384","author":"Sicinski","year":"1996","journal-title":"Nature"},{"key":"2020071613255797600_B46","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/mrd.20788","article-title":"Regulation of NGFI-B\/Nur77 gene expression in the rat ovary and in Leydig tumor cells MA-10.","volume":"75","author":"Inaoka","year":"2008","journal-title":"Mol Reprod Dev"},{"key":"2020071613255797600_B47","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1210\/endo.142.7.8232","article-title":"Gonadotropin regulation of NGFI-B messenger ribonucleic acid expression during ovarian follicle development in the rat.","volume":"142","author":"Park","year":"2001","journal-title":"Endocrinology"},{"key":"2020071613255797600_B48","doi-asserted-by":"crossref","first-page":"12573","DOI":"10.1074\/jbc.M409580200","article-title":"Nur77 regulates lipolysis in skeletal muscle cells. Evidence for cross-talk between the \u03b2-adrenergic and an orphan nuclear hormone receptor pathway.","volume":"280","author":"Maxwell","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071613255797600_B49","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1677\/jme.0.0330059","article-title":"The molecular characteristics of polycystic ovary syndrome (PCOS) ovary defined by human ovary cDNA microarray.","volume":"33","author":"Diao","year":"2004","journal-title":"J Mol Endocrinol"},{"key":"2020071613255797600_B50","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1210\/me.2004-0074","article-title":"Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients.","volume":"18","author":"Jansen","year":"2004","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B51","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1200\/JCO.2002.10.018","article-title":"Molecular biology of the androgen receptor.","volume":"20","author":"Gelmann","year":"2002","journal-title":"J Clin Oncol"},{"key":"2020071613255797600_B52","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1210\/me.2002-0070","article-title":"The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions.","volume":"16","author":"Heinlein","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B53","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.tem.2007.09.004","article-title":"Non-classical actions of testosterone: an update.","volume":"18","author":"Rahman","year":"2007","journal-title":"Trends Endocrinol Metab"},{"key":"2020071613255797600_B54","doi-asserted-by":"crossref","first-page":"37622","DOI":"10.1074\/jbc.M405431200","article-title":"The orphan nuclear receptor NGFIB regulates transcription of 3\u03b2-hydroxysteroid dehydrogenase. implications for the control of adrenal functional zonation.","volume":"279","author":"Bassett","year":"2004","journal-title":"J Biol Chem"},{"key":"2020071613255797600_B55","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/molehr\/gah139","article-title":"The NGFI-B family of transcription factors regulates expression of 3\u03b2-hydroxysteroid dehydrogenase type 2 in the human ovary.","volume":"11","author":"Havelock","year":"2005","journal-title":"Mol Hum Reprod"},{"key":"2020071613255797600_B56","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1210\/me.2004-0043","article-title":"The atypical orphan nuclear receptor DAX-1 interacts with orphan nuclear receptor Nur77 and represses its transactivation.","volume":"18","author":"Song","year":"2004","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B57","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1677\/JME-08-0095","article-title":"The nuclear receptors NUR77 and SF1 play additive roles with c-JUN through distinct elements on the mouse Star promoter.","volume":"42","author":"Martin","year":"2009","journal-title":"J Mol Endocrinol"},{"key":"2020071613255797600_B58","first-page":"321","article-title":"Nuclear receptor coregulators: cellular and molecular biology.","volume":"20","author":"McKenna","year":"1999","journal-title":"Endocr Rev"},{"key":"2020071613255797600_B59","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1210\/me.2010-0367","article-title":"Testosterone, not 5\u03b1-dihydrotestosterone, stimulates LRH-1 leading to FSH-independent expression of Cyp19 and P450scc in granulosa cells.","volume":"25","author":"Wu","year":"2011","journal-title":"Mol Endocrinol"},{"key":"2020071613255797600_B60","first-page":"2414","article-title":"5\u03b1-reductase activity in women with polycystic ovary syndrome.","volume":"84","author":"Jakimiuk","year":"1999","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/26\/12\/2004\/8934491\/mend2004.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/26\/12\/2004\/8934491\/mend2004.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T23:47:59Z","timestamp":1594943279000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/26\/12\/2004\/2614817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,1]]},"references-count":60,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2012,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/me.2012-1200","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,1]]}}}