{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:56:10Z","timestamp":1791114970835,"version":"4.1.0"},"reference-count":27,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese patient with a 46,XY karyotype. Sequence analysis was performed for all the seven exons of SF-1, revealing a heterozygous single base pair deletion at exon 2 (18delC) that is predicted to cause a frameshift at the sixth codon and resultant termination at the 74th codon. Functional studies showed that the mutation produced no demonstrable protein and had no transcription activity or dominant negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly, and psychosexual disturbance. Endocrine studies showed normal adrenal function (cortisol response to ACTH stimulation, 13.4\u219225.3 \u03bcg\/dl) and primary hypogonadism (testosterone response to hCG stimulation, 0.57\u21920.76 ng\/ml; gonadotropin responses to GnRH stimulation: LH, 10\u219259 mIU\/ml; FSH, 36\u219269 mIU\/ml), and urinary steroid hormone profile analysis indicated grossly normal steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.<\/jats:p>","DOI":"10.1210\/jc.2004-0935","type":"journal-article","created":{"date-parts":[[2004,12,3]],"date-time":"2004-12-03T23:47:38Z","timestamp":1102117658000},"page":"5930-5935","source":"Crossref","is-referenced-by-count":86,"title":["Testicular Dysgenesis without Adrenal Insufficiency in a 46,XY Patient with a Heterozygous Inactive Mutation of Steroidogenic Factor-1"],"prefix":"10.1210","volume":"89","author":[{"given":"Tomonobu","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine (T.H., G.S.), Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development (M.F., N.S., N.K., T.O.), Tokyo 154-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development (M.F., N.S., N.K., T.O.), Tokyo 154-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development (M.F., N.S., N.K., T.O.), Tokyo 154-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goro","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine (T.H., G.S.), Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Fukutani","sequence":"additional","affiliation":[{"name":"Department of Urology, Asoka Hospital (K.F.), Tokyo 135-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-Ichirou","family":"Morohashi","sequence":"additional","affiliation":[{"name":"Division of Cell Differentiation, National Institute for Basic Biology (K.-I.M.), Okazaki 444-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development (M.F., N.S., N.K., T.O.), Tokyo 154-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071616443312800_R1","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1096\/fasebj.10.14.9002548","article-title":"Ad4BP\/SF-1, a transcription factor, essential for the transcription of steroidogenic cytochrome P450 genes and for the establishment of the reproductive function.","volume":"10","author":"Morohashi","year":"1996","journal-title":"FASEB J"},{"key":"2020071616443312800_R2","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1210\/edrv.18.3.0301","article-title":"Steroidogenic factor 1: a key determinant of endocrine development and function.","volume":"18","author":"Parker","year":"1997","journal-title":"Endocr Rev"},{"key":"2020071616443312800_R3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S1096-7192(02)00032-X","article-title":"The role of SF1 in adrenal and reproductive function: insight from naturally occurring mutations in humans.","volume":"76","author":"Ozisik","year":"2002","journal-title":"Mol Genet Metab"},{"key":"2020071616443312800_R4","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1210\/endo.143.2.8652","article-title":"Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.","volume":"143","author":"Majdic","year":"2002","journal-title":"Endocrinology"},{"key":"2020071616443312800_R5","doi-asserted-by":"crossref","first-page":"14488","DOI":"10.1073\/pnas.97.26.14488","article-title":"Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response.","volume":"97","author":"Bland","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071616443312800_R6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/9629","article-title":"A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans.","volume":"22","author":"Achermann","year":"1999","journal-title":"Nat Genet"},{"key":"2020071616443312800_R7","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1210\/jcem.87.4.8376","article-title":"Gonadal determination and adrenal development are regulated by the orphan nuclear receptor steroidogenic factor-1, in a dose-dependent manner.","volume":"87","author":"Achermann","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616443312800_R8","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1086\/316893","article-title":"Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1\/SF-1) and adrenocortical insufficiency.","volume":"67","author":"Biason-Lauder","year":"2000","journal-title":"Am J Hum Genet"},{"key":"2020071616443312800_R9","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1210\/jc.2003-031240","article-title":"A microdeletion in the ligand binding domain of human steroidogenic factor 1 causes XY sex reversal without adrenal insufficiency.","volume":"89","author":"Correa","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616443312800_R10","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1507\/endocrj.50.783","article-title":"Reference values for urinary steroids in Japanese newborn infants: gas chromatography\/mass spectrometry in selected ion monitoring.","volume":"50","author":"Homma","year":"2003","journal-title":"Endocr J"},{"key":"2020071616443312800_R11","author":"Hasegawa","year":"2003"},{"key":"2020071616443312800_R12","year":"1996"},{"key":"2020071616443312800_R13","author":"Ujihara","year":"1997"},{"key":"2020071616443312800_R14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.bbrc.2003.10.096","article-title":"Functional characterization of a new human Ad4BP\/SF-1 variation, G146A.","volume":"311","author":"WuQiang","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071616443312800_R15","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/348448a0","article-title":"Genetic evidence equating SRY and the testis-determining factor.","volume":"348","author":"Berta","year":"1990","journal-title":"Nature"},{"key":"2020071616443312800_R16","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1210\/jcem.86.6.7539","article-title":"Absence of mutations involving the LIM homeobox domain gene LHX9 in 46,XY gonadal agenesis and dysgenesis.","volume":"86","author":"Ottolenghi","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616443312800_R17","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/hmg\/8.6.989","article-title":"A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators.","volume":"8","author":"Raymond","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2020071616443312800_R18","first-page":"643","article-title":"Functional difference between Ad4BP and ELP, and their distributions in steroidogenic tissues.","volume":"8","author":"Morohashi","year":"1994","journal-title":"Mol Endocrinol"},{"key":"2020071616443312800_R19","doi-asserted-by":"crossref","first-page":"4585","DOI":"10.1074\/jbc.273.8.4585","article-title":"Regulation of the human P450scc gene by steroidogenic factor 1 is mediated by CBP\/p300.","volume":"273","author":"Monte\u0301","year":"1998","journal-title":"J Biol Chem"},{"key":"2020071616443312800_R20","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/jc.2002-021034","article-title":"An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.","volume":"88","author":"Ozisik","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071616443312800_R21","doi-asserted-by":"crossref","first-page":"31708","DOI":"10.1074\/jbc.M002892200","article-title":"A naturally occurring steroidogenic factor-1 mutation exhibits differential binding and activation of target genes.","volume":"275","author":"Ito","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071616443312800_R22","first-page":"842","article-title":"Disorders of sex differentiation","author":"Grumbach","year":"2002","journal-title":"In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams textbook of endocrinology. 10th ed. Philadelphia: Saunders;"},{"key":"2020071616443312800_R23","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/ng0594-5","article-title":"Human haploinsufficiency: one for sorrow, two for joy.","volume":"7","author":"Fisher","year":"1994","journal-title":"Nat Genet"},{"key":"2020071616443312800_R24","first-page":"478","article-title":"The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus.","volume":"9","author":"Ikeda","year":"1995","journal-title":"Mol Endocrinol"},{"key":"2020071616443312800_R25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0950-351X(98)80191-2","article-title":"Androgens and abdominal obesity.","volume":"12","author":"Marin","year":"1998","journal-title":"Baillieres Clin Endocrinol Metab"},{"key":"2020071616443312800_R26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/cne.903480103","article-title":"Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat.","volume":"348","author":"Canteras","year":"1994","journal-title":"J Comp Neurol"},{"key":"2020071616443312800_R27","first-page":"2815","article-title":"Immunohistochemical localization of Ad4-binding protein with correlation to steroidogenic enzyme expression in cycling human ovaries and sex cord stromal tumors.","volume":"80","author":"Takayama","year":"1995","journal-title":"J Clin Endocrinol Metab"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/89\/12\/5930\/10772861\/jcem5930.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/89\/12\/5930\/10772861\/jcem5930.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T03:24:04Z","timestamp":1594956244000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/89\/12\/5930\/2844172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,1]]},"references-count":27,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2004,12,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2004-0935","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,1]]}}}