{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:06:12Z","timestamp":1785535572437,"version":"3.56.0"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Testicular adrenal rest tumors (TART) are a frequent and fertility impairing\n                    long-term complication in males with classic congenital adrenal hyperplasia. Due\n                    to lack of clear experimental data on their origin, they are hypothesized to be\n                    derived from ectopic adrenocortical cells within testicular tissue mainly\n                    growing upon stimulation by chronically elevated levels of adrenocorticotropin\n                    (ACTH). Alternatively, a more totipotent embryological origin has been discussed\n                    as the potential source of these tumors. The aim of this study was to quantify\n                    alterations of ectopic expression of adrenocortical genes (CYP11B1, CYP11B2,\n                    CYP21, MC2R) and the Leydig cell specific marker (INSL3) in testicular tissue of\n                    fetal 21-hydroxylase deficient (21OHD) mice. Timed-pregnancy studies were\n                    performed using H-2aw18 (aw18)-mice. Testes and adrenals of E15.5 and E18.5\n                    mouse fetuses were used for real-time PCR and immunohistochemistry. Gene\n                    expression levels were analyzed for genotype-dependent alterations and compared\n                    with immunohistochemistry. While enzymes of steroidogenesis showed a significant\n                    increased expression in adrenals of 21OHD mice at both E15.5 and E18.5 compared\n                    to wild-type (WT) mice, expression levels were unaltered in testes of 21OHD\n                    mice. When compared to WT adrenals a significant increase of INSL3 expression in\n                    adrenals of 21OHD mice at E15.5 and E18.5 was detected. Cells with\n                    adrenocortical properties in mice fetal testis differ from in situ\n                    adrenocortical cells in gene expression and growth at E15.5 and E18.5. These\n                    findings suggest that the different local regulation and different local niche\n                    in adrenals and testes influence growth of aberrant adrenal cells.<\/jats:p>","DOI":"10.1055\/a-2216-0269","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T23:32:57Z","timestamp":1704324777000},"page":"38-44","source":"Crossref","is-referenced-by-count":2,"title":["Quantitative Characterization of Ectopic Adrenal Gene Expression in\n                    Fetal Testes in 21-Hydroxylase Deficient Mice"],"prefix":"10.1055","volume":"56","author":[{"given":"Maximilian","family":"Weniger","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum M\u00fcnchen, Munich,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mattes","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum M\u00fcnchen, Munich,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.P.","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Max Eder Research Group for Pediatric Sarcoma Biology, Institute of\n                    Pathology, LMU Klinikum M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Children's Hospital, Medizinische\n                    Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden,\n                    Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"H\u00fcbner","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Children's Hospital, Medizinische\n                    Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden,\n                    Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3984","authenticated-orcid":false,"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum M\u00fcnchen, Munich,\n                    Germany"},{"name":"Klinik f\u00fcr Endokrinologie, Diabetologie und Klinische\n                    Ern\u00e4hrung, Universit\u00e4tsSpital Z\u00fcrich, Z\u00fcrich,\n                    Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV, LMU Klinikum M\u00fcnchen, Munich,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,1,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an\n                    endocrine society clinical practice guideline","volume":"103","author":"P W Speiser","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0140-6736(22)01330-7","article-title":"Congenital adrenal hyperplasia","volume":"401","author":"M K Auer","year":"2023","journal-title":"Lancet"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5721","DOI":"10.1210\/jcem.86.12.8090","article-title":"High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and\n                    Leydig cell failure in adolescent and adult males with congenital adrenal\n                    hyperplasia","volume":"86","author":"N M Stikkelbroeck","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1210\/jc.2008-1414","article-title":"High prevalence of reduced fecundity in men with congenital adrenal\n                    hyperplasia","volume":"94","author":"N Reisch","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1210\/jc.2014-4124","article-title":"Clinical outcome, hormonal status, gonadotrope axis, and testicular function in\n                    219 adult men born with classic 21-hydroxylase deficiency. A French national\n                    survey","volume":"100","author":"C Bouvattier","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1210\/jc.2010-0917","article-title":"Health status of adults with congenital adrenal hyperplasia: a cohort study of\n                    203 patients","volume":"95","author":"W Arlt","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1530\/EJE-17-0862","article-title":"Gonadal function in adult male patients with congenital adrenal hyperplasia","volume":"178","author":"M Engels","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.1210\/jc.2007-0337","article-title":"Testicular tumors in patients with congenital adrenal hyperplasia due to\n                    21-hydroxylase deficiency show functional features of adrenocortical tissue","volume":"92","author":"H L Claahsen-van der Grinten","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"E524","DOI":"10.1210\/jc.2014-2036","article-title":"Molecular characterization of testicular adrenal rest tumors in congenital\n                    adrenal hyperplasia; lesions with both adrenocortical and Leydig cell\n                    features","volume":"100","author":"E E Smeets","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.beem.2008.09.007","article-title":"Testicular adrenal rest tumours in congenital adrenal hyperplasia","volume":"23","author":"H L Claahsen-van der Grinten","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ydbio.2006.07.030","article-title":"Identification of a novel population of adrenal-like cells in the mammalian\n                    testis","volume":"299","author":"P Val","year":"2006","journal-title":"Develop Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1111\/j.1365-2605.2009.00967.x","article-title":"Testicular adrenal rest tumours in boys, adolescents and adult men with\n                    congenital adrenal hyperplasia may be associated with the CYP21A2 mutation","volume":"33","author":"A Mouritsen","year":"2010","journal-title":"Int J Androl"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1073\/pnas.84.9.2819","article-title":"Lethal deletion of the complement component C4 and steroid 21-hydroxylase genes\n                    in the mouse H-2 class III region, caused by meiotic recombination","volume":"84","author":"T Shiroishi","year":"1987","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1210\/en.2004-1563","article-title":"Congenital adrenal hyperplasia: the molecular basis of 21-hydroxylase deficiency\n                    in H-2(aw18) mice","volume":"146","author":"F G Riepe","year":"2005","journal-title":"Endocrinology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1046\/j.1365-2443.1996.00254.x","article-title":"Identical origin of adrenal cortex and gonad revealed by expression profiles of\n                    Ad4BP\/SF-1","volume":"1","author":"O Hatano","year":"1996","journal-title":"Genes Cells"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1242\/dev.117.1.273","article-title":"Mesonephric contribution to testis differentiation in the fetal mouse","volume":"117","author":"M Buehr","year":"1993","journal-title":"Development"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1101\/gad.981202","article-title":"Desert hedgehog\/patched 1 signaling specifies fetal Leydig cell fate in\n                    testis organogenesis","volume":"16","author":"H H Yao","year":"2002","journal-title":"Genes Develop"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1101\/gad.1052503","article-title":"Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development\n                    in the XY gonad","volume":"17","author":"J Brennan","year":"2003","journal-title":"Genes Develop"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/ng1009","article-title":"Mutation of ARX causes abnormal development of forebrain and testes in mice and\n                    X-linked lissencephaly with abnormal genitalia in humans","volume":"32","author":"K Kitamura","year":"2002","journal-title":"Nat Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1210\/me.2002-0055","article-title":"Steroid deficiency syndromes in mice with targeted disruption of Cyp11a1","volume":"16","author":"M C Hu","year":"2002","journal-title":"Mol Endocrinol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1210\/en.2003-0277","article-title":"Adrenocorticotropic hormone directly stimulates testosterone production by the\n                    fetal and neonatal mouse testis","volume":"144","author":"P J O'Shaughnessy","year":"2003","journal-title":"Endocrinology"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1530\/REP-06-0359","article-title":"Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal\n                    mouse testis","volume":"133","author":"H Johnston","year":"2007","journal-title":"Reproduction"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1530\/REP-07-0133","article-title":"Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis","volume":"134","author":"L Hu","year":"2007","journal-title":"Reproduction"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1530\/REP-10-0365","article-title":"Endocrinology of the mammalian fetal testis","volume":"141","author":"P J O'Shaughnessy","year":"2011","journal-title":"Reproduction"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1530\/rep.0.1220227","article-title":"Role of gonadotrophins in regulating numbers of Leydig and Sertoli cells during\n                    fetal and postnatal development in mice","volume":"122","author":"P J Baker","year":"2001","journal-title":"Reproduction"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1046\/j.1432-1327.1999.00245.x","article-title":"Expression of 3beta-hydroxysteroid dehydrogenase type I and type VI isoforms in\n                    the mouse testis during development","volume":"260","author":"P J Baker","year":"1999","journal-title":"Eur J Biochem\/FEBS"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1530\/jrf.0.0930233","article-title":"Proliferative activity of gonocytes, Sertoli cells and interstitial cells during\n                    testicular development in mice","volume":"93","author":"R P Vergouwen","year":"1991","journal-title":"J Reprod Fertil"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1210\/mend.15.1.0582","article-title":"Normal prenatal but arrested postnatal sexual development of luteinizing hormone\n                    receptor knockout (LuRKO) mice","volume":"15","author":"F P Zhang","year":"2001","journal-title":"Mol Endocrinol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1210\/en.2002-220052","article-title":"Pituitary hormones are not required for sexual differentiation of male mice:\n                    phenotype of the T\/ebp\/Nkx2.1 null mutant mice","volume":"143","author":"P Pakarinen","year":"2002","journal-title":"Endocrinology"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1210\/mend.15.1.0586","article-title":"Targeted disruption of luteinizing hormone\/human chorionic gonadotropin\n                    receptor gene","volume":"15","author":"Z M Lei","year":"2001","journal-title":"Mol Endocrinol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1210\/en.2002-220275","article-title":"Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone\n                    production","volume":"143","author":"M Heikkila","year":"2002","journal-title":"Endocrinology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1210\/jc.2009-1929","article-title":"Total adrenal volume but not testicular adrenal rest tumor volume is associated\n                    with hormonal control in patients with 21-hydroxylase deficiency","volume":"95","author":"N Reisch","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"E1820","DOI":"10.1210\/jc.2012-3181","article-title":"Testicular adrenal rest tumors develop independently of long-term disease\n                    control: a longitudinal analysis of 50 adult men with congenital adrenal\n                    hyperplasia due to classic 21-hydroxylase deficiency","volume":"98","author":"N Reisch","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1210\/jc.2016-3989","article-title":"11-Oxygenated androgens are biomarkers of adrenal volume and testicular adrenal\n                    rest tumors in 21-hydroxylase deficiency","volume":"102","author":"A F Turcu","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1210\/endo.140.7.6755","article-title":"Prenatal dexamethasone treatment does not prevent alterations of the\n                    hypothalamic pituitary adrenal axis in steroid 21-hydroxylase deficient\n                    mice","volume":"140","author":"T Tajima","year":"1999","journal-title":"Endocrinology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mce.2014.09.029","article-title":"Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and\n                    ferret","volume":"399","author":"M Schillebeeckx","year":"2015","journal-title":"Mol Cell Endocrinol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2011.09.045","article-title":"Animal models of adrenocortical tumorigenesis","volume":"351","author":"F Beuschlein","year":"2012","journal-title":"Mol Cell Endocrinol"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2216-0269.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:21:49Z","timestamp":1730812909000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2216-0269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":37,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2024,1,3]]},"published-print":{"date-parts":[[2024,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2216-0269","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]}}}