{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:50:15Z","timestamp":1778644215134,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H06428"],"award-info":[{"award-number":["17H06428"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20ek0109464"],"award-info":[{"award-number":["JP20ek0109464"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>It is widely believed that adrenal tumours and ovarian luteomas in pregnant women cause virilisation of female foetuses through overproduction of testosterone and\/or androstenedione. However, this notion raises a fundamental question as to how these classic androgens pass through the placenta without being converted by aromatase into oestrogens. Here, we report a case of maternal adrenal tumour, in which overproduction of 11-oxygenated C19 steroids (11ox C19s), newly characterised non-aromatisable androgens in humans, caused foetal virilisation. The female proband presented with severely virilised external genitalia at birth. The mother exhibited hirsutism, hyperglycaemia and hypertension and was diagnosed as having adrenal tumour. The mother was subjected to comprehensive steroid measurement. Serum levels of 11ox C19s were markedly elevated. In contrast, testosterone and androstenedione levels remained within the normal range, and levels of most other steroids in the conventional and backdoor androgenic pathways were normal or only mildly elevated. After tumour removal, levels of 11ox C19s were markedly reduced. These results provide the first evidence that 11ox C19s can be synthesised in adrenal adenomas and, due to their non-aromatisable nature, can pass through the placental barrier to cause foetal virilisation. These findings highlight a unique pathogenic property of these newly specified androgens in humans.<\/jats:p>","DOI":"10.1093\/humrep\/deaa221","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T15:38:05Z","timestamp":1596728285000},"page":"2609-2612","source":"Crossref","is-referenced-by-count":13,"title":["Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour"],"prefix":"10.1093","volume":"35","author":[{"given":"Keisuke","family":"Nagasaki","sequence":"first","affiliation":[{"name":"Division of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Yamagata 990-2331, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikahiko","family":"Numakura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yamagata University School of Medicine, Yamagata 990-2331, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Homma","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Keio University Hospital, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-0074, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,8,30]]},"reference":[{"key":"2020111005432633300_deaa221-B1","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1515\/JPEM.2004.17.11.1571","article-title":"Female pseudohermaphroditism with phallic urethra in the offspring of a mother with an adrenal tumor","volume":"17","author":"Alvarez-Nava","year":"2004","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2020111005432633300_deaa221-B2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/dvdy.23892","article-title":"Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development","volume":"242","author":"Fukami","year":"2013","journal-title":"Dev Dyn"},{"key":"2020111005432633300_deaa221-B3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1365-2265.1983.tb03197.x","article-title":"An adrenal adenoma causing virilization of mother and infant","volume":"18","author":"Fuller","year":"1983","journal-title":"Clin Endocrinol"},{"key":"2020111005432633300_deaa221-B4","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1210\/jc.2016-2311","article-title":"11-Ketotestosterone is a major androgen produced in human gonads","volume":"101","author":"Imamichi","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"2020111005432633300_deaa221-B5","doi-asserted-by":"crossref","first-page":"E367","DOI":"10.1210\/jc.2011-1997","article-title":"Increased activation of the alternative \u201cbackdoor\u201d pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis","volume":"97","author":"Kamrath","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020111005432633300_deaa221-B6","doi-asserted-by":"crossref","first-page":"243","DOI":"10.33549\/physiolres.932078","article-title":"Hyperandrogenic states in pregnancy","volume":"60","author":"Ka\u0148ov\u00e1","year":"2011","journal-title":"Physiol Res"},{"key":"2020111005432633300_deaa221-B7","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1210\/jcem-70-5-1280","article-title":"Female pseudohermaphroditism due to a maternal adrenocortical tumor","volume":"70","author":"Kirk","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"key":"2020111005432633300_deaa221-B8","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1530\/acta.0.0650627","article-title":"Male external genitalia of a girl caused by a virilizing adrenal tumour in the mother. 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