{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:53:49Z","timestamp":1791219229765,"version":"4.1.0"},"reference-count":25,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2018,12,22]],"date-time":"2018-12-22T00:00:00Z","timestamp":1545436800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health"},{"DOI":"10.13039\/501100003554","name":"Lundbeckfonden","doi-asserted-by":"publisher","award":["R249-2017-1484"],"award-info":[{"award-number":["R249-2017-1484"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["098522"],"award-info":[{"award-number":["098522"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Setting<\/jats:title>\n                  <jats:p>Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measure(s)<\/jats:title>\n                  <jats:p>Expression level of steroidogenic genes and protein expression\/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS\/MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1\/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P &amp;lt; 0.05), whereas expression levels of 3\u03b2-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3\u03b2-HSD1\/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng\/g tissue), and testosterone levels were the lowest (2 to 14 ng\/g tissue).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2018-01759","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T19:20:32Z","timestamp":1545420032000},"page":"1802-1812","source":"Crossref","is-referenced-by-count":43,"title":["Characterization of Human Adrenal Steroidogenesis During Fetal Development"],"prefix":"10.1210","volume":"104","author":[{"given":"Cecilie","family":"Melau","sequence":"first","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Erik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Frederiksen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Kilcoyne","sequence":"additional","affiliation":[{"name":"MRC Centre for Reproductive Health, The Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, University Hospital of Copenhagen (Rigshospitalet), Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene","family":"Lundvall","sequence":"additional","affiliation":[{"name":"Department of Gynaecology, University Hospital of Copenhagen (Rigshospitalet), Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Langhoff Thuesen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Juul Hare","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Hvidovre University Hospital, Hvidovre, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Maria","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"},{"name":"International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod T","family":"Mitchell","sequence":"additional","affiliation":[{"name":"MRC Centre for Reproductive Health, The Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Juul","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, 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