{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:45:58Z","timestamp":1791812758354,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hydroxysteroid (17\u03b2) dehydrogenase type 3 (HSD17B3) deficiency causes a disorder of sex development in humans, where affected males are born with female\u2010appearing external genitalia, but are virilized during puberty. The hormonal disturbances observed in the\n                    <jats:italic>Hsd17b3<\/jats:italic>\n                    knockout mice (HSD17B3KO), generated in the present study, mimic those found in patients with\n                    <jats:italic>HSD17B3<\/jats:italic>\n                    mutations. Identical to affected humans, serum T in the adult HSD17B3KO mice was within the normal range, while a striking increase was detected in serum A\u2010dione concentration. This resulted in a marked reduction of the serum T\/A\u2010dione ratio, a diagnostic hallmark for the patients with HSD17B3 deficiency. However, unlike humans, male HSD17B3KO mice were born with normally virilized phenotype, but presenting with delayed puberty. In contrast to the current belief, data from HSD17B3KO mice show that the circulating T largely originates from the testes, indicating a strong compensatory mechanism in the absence of HSD17B3. The lack of testicular malignancies in HSD17B3KO mice supports the view that testis tumors in human patients are due to associated cryptorchidism. The HSD17B3KO mice presented also with impaired Leydig cell maturation and signs of undermasculinization in adulthood. The identical hormonal disturbances between HSD17B3 deficient knockout mice and human patients make the current mouse model valuable for understanding the mechanism of the patient phenotypes, as well as endocrinopathies and compensatory steroidogenic mechanisms in HSD17B3 deficiency.\n                  <\/jats:p>","DOI":"10.1096\/fj.201902384r","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T08:08:59Z","timestamp":1584605339000},"page":"6111-6128","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency"],"prefix":"10.1096","volume":"34","author":[{"given":"P.","family":"Sipil\u00e4","sequence":"first","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"},{"name":"Turku Center for Disease Modeling (TCDM) Institute of Biomedicine University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Junnila","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hakkarainen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Mairinoja","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. P.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"},{"name":"Turku Center for Disease Modeling (TCDM) Institute of Biomedicine University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Ohlsson","sequence":"additional","affiliation":[{"name":"Institute of Medicine the Sahlgrenska Academy Gothenburg University Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Kotaja","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Poutanen","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Research Centre for Integrative Physiology and Pharmacology University of Turku Turku Finland"},{"name":"Turku Center for Disease Modeling (TCDM) Institute of Biomedicine University of Turku Turku Finland"},{"name":"Institute of Medicine the Sahlgrenska Academy Gothenburg University Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0315"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1210\/endo.141.7.7545","article-title":"Localization of 17\u03b2\u2010hydroxysteroid dehydrogenase\/17\u2010ketosteroid reductase isoform expression in the developing mouse testis\u2014androstenedione is the major androgen secreted by fetal\/neonatal leydig cells","volume":"141","author":"O'shaughnessy PJ","year":"2000","journal-title":"Endocrinology"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.1.187"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.1999.00363.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2012-1256"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmv008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320735111"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2018.11.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.08.012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.05.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.12.4713"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(92)90327-F"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000318004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7111"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod17.2.298"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035538"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1204-249"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700921R"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod62.4.886"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.132.4.8462469"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1890"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.2.802"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.07.029"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00196"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.00482.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220052"},{"key":"e_1_2_9_28_1","first-page":"28","article-title":"Transgenic and knockout mouse models for aberrant pituitary\u2010testicular function: relevance to the pathogenesis of cryptorchidism","volume":"46","author":"Huhtaniemi I","year":"2004","journal-title":"Turk J Pediatr"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.11.4652"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.1.0582"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1586\/17446651.4.1.53"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017-00285"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-2760(96)00034-3"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-68-2-477"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000336605"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-108-6-2142"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-005-0006-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2006.098319"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-200009000-00003"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1210\/jcem-51-6-1293","article-title":"17\u03b2\u2010hydroxysteroid dehydrogenase deficiency in malignant interstitial cell carcinoma of the testis","volume":"51","author":"Davis S","year":"1980","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-49-3-391"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0139"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0029-0"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00255915"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-255729"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037064"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.201902384R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902384R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201902384R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201902384R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:01:13Z","timestamp":1761692473000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201902384R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,19]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1096\/fj.201902384R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201902384r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,19]]},"assertion":[{"value":"2019-09-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}