{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:12:26Z","timestamp":1791353546392,"version":"4.3.1"},"reference-count":42,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2001,1,15]],"date-time":"2001-01-15T00:00:00Z","timestamp":979516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Knockout mice lacking the orphan nuclear receptor steroidogenic factor 1 (SF1) exhibit a complex endocrine phenotype that includes adrenal and gonadal agenesis, impaired expression of pituitary gonadotropins, and absence of the ventromedial hypothalamic nucleus (VMH). These multiple defects complicate efforts to delineate primary versus secondary effects of SF1 deficiency in different tissues, such that its direct role in gonadotropes remains uncertain. To define this role, we have expressed Cre recombinase driven by the promoter region of the common \u03b1 subunit of glycoprotein hormones (\u03b1GSU), thereby inactivating a loxP-modified SF1 locus in the anterior pituitary gland. Although pituitary-specific SF1 knockout mice were fully viable, they were sterile and failed to develop normal secondary sexual characteristics.<\/jats:p>\n               <jats:p>Their adrenal glands and VMH appeared normal histologically, but their testes and ovaries were severely hypoplastic. \u03b1GSU-Cre, loxP mice had normal levels of most pituitary hormones, but had markedly decreased expression of LH and FSH. Treatment with exogenous gonadotropins stimulated gonadal steroidogenesis, inducing germ cell maturation in males and follicular and uterine maturation in females \u2013 establishing that the gonads can respond to gonadotropins. The pituitary-specific SF1 knockout mice are a novel genetic model of hypogonadotropic hypogonadism that establishes essential role(s) of SF1 in pituitary gonadotropes.<\/jats:p>","DOI":"10.1242\/dev.128.2.147","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T05:59:29Z","timestamp":1619416769000},"page":"147-154","source":"Crossref","is-referenced-by-count":188,"title":["Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function"],"prefix":"10.1242","volume":"128","author":[{"given":"Liping","family":"Zhao","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Departments of Internal Medicine and Pharmacology , , Dallas, TX 75390-8857, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Bakke","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Departments of Internal Medicine and Pharmacology , , Dallas, TX 75390-8857, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Krimkevich","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Departments of Internal Medicine and Pharmacology , , Dallas, TX 75390-8857, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Cushman","sequence":"additional","affiliation":[{"name":"University of Michigan 2 Department of Human Genetics , , Ann Arbor, MI 48109-0638, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F.","family":"Parlow","sequence":"additional","affiliation":[{"name":"3 Harbor-UCLA Medical Center, Torrance, CA 90509-2006, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally A.","family":"Camper","sequence":"additional","affiliation":[{"name":"University of Michigan 2 Department of Human Genetics , , Ann Arbor, MI 48109-0638, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith L.","family":"Parker","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Departments of Internal Medicine and Pharmacology , , Dallas, TX 75390-8857, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2001,1,15]]},"reference":[{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1210\/endo.141.5.7456","article-title":"The effect of a null mutation in the follicle-stimulating hormone receptor gene on mouse reproduction","volume":"141","author":"Abel","year":"2000","journal-title":"Endocrinology"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/9629","article-title":"A mutation in the gene encoding steroidogenic factor-1 causes 46,XY sex reversal and adrenal failure in humans","volume":"22","author":"Achermann","year":"1999","journal-title":"Nat. Genet"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1210\/mend.13.6.0301","article-title":"Fertility and infertility: genetic contributions from the hypothalamic-pituitary-gonadal axis","volume":"13","author":"Achermann","year":"1999","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1056\/NEJM199903043400907","article-title":"Single-gene mutations resulting in reproductive dysfunction in women","volume":"340","author":"Adashi","year":"1999","journal-title":"New Engl. J. Med"},{"key":"2023022722552390400_","first-page":"878","article-title":"The orphan nuclear receptor steroidogenic factor 1 regulates the glycoprotein hormone \u03b1-subunit gene in pituitary gonadotrophs","volume":"8","author":"Barnhart","year":"1994","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S1357-2725(97)00082-4","article-title":"Steroidogenic factor-1 (SF-1) and the regulation of expression of luteinising hormone and follicle stimulating hormone \u03b2-subunits in the sheep anterior pituitary in vivo","volume":"29","author":"Brown","year":"1997","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S1043-2760(99)00189-7","article-title":"Geneology of the anterior pituitary: tracing a family tree","volume":"10","author":"Burrows","year":"1999","journal-title":"Trends Endocrinol. Metab"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1210\/mend.11.11.9970","article-title":"The activation function-2 hexamer of steroidogenic factor-1 is required but not sufficient for potentiation by SRC-1","volume":"11","author":"Crawford","year":"1997","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","article-title":"Cre-mediated recombination in the pituitary gland","volume-title":"Genesis","author":"Cushman","year":"2001"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S0955-0674(99)00034-4","article-title":"Signaling mechanisms in pituitary morphogenesis and cell fate determination","volume":"11","author":"Dasen","year":"1999","journal-title":"Curr. Opin. Cell. Bio"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/S0092-8674(00)80770-9","article-title":"Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient induced determination of pituitary cell types","volume":"97","author":"Dasen","year":"1999","journal-title":"Cell"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"13612","DOI":"10.1073\/pnas.95.23.13612","article-title":"Imparing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance","volume":"95","author":"Dierich","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"13870","DOI":"10.1074\/jbc.274.20.13870","article-title":"Activation of luteinizing hormone beta gene by gonadotropin-releasing hormone requires the synergy of early growth response-1 and steroidogenic factor-1","volume":"274","author":"Dorn","year":"1999","journal-title":"J. Biol. Chem"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1095\/biolreprod56.1.160","article-title":"A binding site for steroidogenic factor-1 is part of a complex enhancer that mediates expression of the murine gonadotropin-releasing hormone receptor gene","volume":"56","author":"Duval","year":"1997","journal-title":"Biol. Reprod"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"6645","DOI":"10.1074\/jbc.271.12.6645","article-title":"Stimulation of luteinizing hormone \u03b2 gene promoter activity by the orphan nuclear receptor, steroidogenic factor-1 J","volume":"271","author":"Halvorson","year":"1996","journal-title":"Biol. Chem"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"14712","DOI":"10.1074\/jbc.273.24.14712","article-title":"Steroidogenic factor-1 and early growth response protein 1 act through two composite DNA binding sites to regulate luteinizing hormone beta-subunit","volume":"273","author":"Halvorson","year":"1998","journal-title":"J. Biol. Chem"},{"key":"2023022722552390400_","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":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.1101\/gad.8.19.2302","article-title":"The nuclear receptor SF-1 acts at multiple levels of the reproductive axis","volume":"8","author":"Ingraham","year":"1994","journal-title":"Genes Dev"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1210\/mend.12.2.0059","article-title":"Steroidogenic factor 1 contains a carboxy-terminal transcriptional activation domain that interacts with steroid receptor coactivator-1","volume":"12","author":"Ito","year":"1998","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1177\/42.8.8027530","article-title":"In situ hybridization analysis of anterior pituitary hormone gene expression during fetal mouse development","volume":"42","author":"Japon","year":"1994","journal-title":"J. Histochem. Cytochem"},{"key":"2023022722552390400_","first-page":"1420","article-title":"Enhancer-mediated high level expression of mouse pituitary glycoprotein hormone alpha-subunit transgene in thyrotropes, gonadotropes, and developing pituitary","volume":"8","author":"Kendall","year":"1994","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1101\/gad.9.16.2007","article-title":"Targeted disruption of the pituitary glycoprotein hormone alpha-subunit produces hypogonadal and hypothyroid mice","volume":"9","author":"Kendall","year":"1995","journal-title":"Genes Dev"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1210\/mend-5-12-2025","article-title":"Targeted ablation of pituitary gonadotropes in transgenic mice","volume":"5","author":"Kendall","year":"1991","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"10782","DOI":"10.1074\/jbc.271.18.10782","article-title":"A steroidogenic factor 1 binding site is required for activity of the luteinizing hormone beta subunit promoter in gonadotropes of transgenic mice","volume":"271","author":"Keri","year":"1996","journal-title":"J Biol. Chem"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/ng0297-201","article-title":"Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility","volume":"15","author":"Kumar","year":"1997","journal-title":"Nat. Genet"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0303-7207(97)00184-6","article-title":"Presence of distinct cis-acting elements on gonadotropin gene promoters in diverse species dictates the selective recruitment of different transcription factors by steroidogenic factor-1","volume":"135","author":"Le Drean","year":"1997","journal-title":"Mol. Cell. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1126\/science.273.5279.1219","article-title":"Luteinizing hormone deficiency and female infertility in mice lacking the transcription factor NGFI-A (Egr-1","volume":"273","author":"Lee","year":"1996","journal-title":"Science"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/0092-8674(94)90211-9","article-title":"A cell specific nuclear receptor is required for adrenal and gonadal development and for male sexual differentiation","volume":"77","author":"Luo","year":"1994","journal-title":"Cell"},{"key":"2023022722552390400_","first-page":"1233","article-title":"Steroidogenic factor 1 is the essential transcript encoded by the mouse Ftz-F1 gene","volume":"9","author":"Luo","year":"1995","journal-title":"Mol. Endocrinol"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1172\/JCI118634","article-title":"Recent advances in gene mutagenesis by site-directed recombination","volume":"97","author":"Marth","year":"1996","journal-title":"J Clin Invest"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1126\/science.3024317","article-title":"A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse","volume":"234","author":"Mason","year":"1986","journal-title":"Science"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","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":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/(SICI)1526-968X(200002)26:2&lt;99::AID-GENE1&gt;3.0.CO;2-B","article-title":"Cre recombinase: the universal reagent for genome tailoring","volume":"26","author":"Nagy","year":"2000","journal-title":"Genesis"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"2452","DOI":"10.1210\/endo.140.6.6759","article-title":"Steroidogenic factor-1 interacts with a gonadotrope-specific element within the first exon of the human gonadotropin-releasing hormone receptor gene to mediate gonadotrope-specific expression","volume":"140","author":"Ngan","year":"1999","journal-title":"Endocrinology"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1093\/oxfordjournals.jbchem.a124918","article-title":"Genomic organization and isoforms of the mouse ELP gene","volume":"118","author":"Ninomiya","year":"1995","journal-title":"J. Biochem. (Tokyo)"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1210\/endo.139.3.5788","article-title":"Fetal development of Leydig cell activity is independent of pituitary gonadotroph function","volume":"139","author":"O\u2019Shaughnessy","year":"1998","journal-title":"Endocrinology"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","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":"Endocrine Rev"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"10939","DOI":"10.1073\/pnas.92.24.10939","article-title":"Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids","volume":"92","author":"Sadovsky","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023022722552390400_","first-page":"381","article-title":"Inducible gene targeting in mice using the Cre-lox system. Methods","volume":"14","author":"Sauer","year":"1998"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/aja.1002040104","article-title":"Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1-disrupted mice","volume":"204","author":"Shinoda","year":"1995","journal-title":"Dev. Dyn"},{"key":"2023022722552390400_","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1128\/MCB.19.4.2567","article-title":"Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene expression","volume":"19","author":"Tremblay","year":"1999","journal-title":"Mol Cell. Biol"},{"key":"2023022722552390400_","first-page":"1497","article-title":"The equine luteinizing hormone beta-subunit promoter contains two functional steroidogenic factor-1 response elements","volume":"13","author":"Wolfe","year":"1999","journal-title":"Mol Endocrinol"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/128\/2\/147\/2542238\/develop_128_2_147.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/128\/2\/147\/2542238\/develop_128_2_147.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T22:55:26Z","timestamp":1677538526000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/128\/2\/147\/41380\/Steroidogenic-factor-1-SF1-is-essential-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,1,15]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2001,1,15]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.128.2.147","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,1,15]]}}}