{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:43:17Z","timestamp":1790872997936,"version":"4.1.0"},"reference-count":48,"publisher":"Cold Spring Harbor Laboratory","issue":"17","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1997,9,1]]},"abstract":"<jats:p>A large number of intercellular signaling molecules have been identified that orchestrate female reproductive physiology. However, with the exception of steroid hormone receptors, little information exists about the transcriptional regulators that mediate cellular responses to these signals. The transcription factor C\/EBP\u03b2 (<jats:underline>C<\/jats:underline>CAAT\/<jats:underline>e<\/jats:underline>nhancer-<jats:underline>b<\/jats:underline>inding<jats:underline>p<\/jats:underline>rotein <jats:underline>\u03b2<\/jats:underline>) is expressed in ovaries and testes, as well as many other tissues of adult mice. Here we show that mice carrying a targeted deletion of the C\/EBP\u03b2 gene exhibit reproductive defects. Although these animals develop normally and males are fertile, adult females are sterile. Transplantation of normal ovaries into mutant females restored fertility, thus localizing the primary reproductive defect to the ovary proper. In normal ovaries, C\/EBP\u03b2 mRNA is specifically induced by luteinizing hormone (LH\/hCG) in the granulosa layer of preovulatory antral follicles. C\/EBP\u03b2-deficient ovaries lack corpora lutea and fail to down-regulate expression of the prostaglandin endoperoxidase synthase 2 and P450 aromatase genes in response to gonadotropins. These findings demonstrate that C\/EBP\u03b2 is essential for periovulatory granulosa cell differentiation in response to LH. C\/EBP\u03b2 is thus established as a critical downstream target of G-protein-coupled LH receptor signaling and one of the first transcription factors, other than steroid hormone receptors, known to be required for ovarian follicle development in vivo.<\/jats:p>","DOI":"10.1101\/gad.11.17.2153","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:15:26Z","timestamp":1203545726000},"page":"2153-2162","source":"Crossref","is-referenced-by-count":317,"title":["An essential role for C\/EBP\u03b2 in female\u2009reproduction"],"prefix":"10.1101","volume":"11","author":[{"given":"Esta","family":"Sterneck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lino","family":"Tessarollo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1997,9,1]]},"reference":[{"key":"2021111418470262000_11.17.2153.1","unstructured":"Adashi E.Y. Leung P.C.K. (1993) The ovary. in Comprehensive endocrinology, ed Martini L. (Raven Press, New York, NY)."},{"key":"2021111418470262000_11.17.2153.2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1000300303"},{"key":"2021111418470262000_11.17.2153.3","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.3.465"},{"key":"2021111418470262000_11.17.2153.4","doi-asserted-by":"publisher","DOI":"10.1042\/bst0230929"},{"key":"2021111418470262000_11.17.2153.5","doi-asserted-by":"crossref","unstructured":"Cunliffe-Beamer T.L. (1983) Biomethodology and surgical techniques. in The mouse in biomedical research, eds Foster H.L. Small J.D. Fox J.G. (Academic Press, New York, NY), pp 401\u2013437.","DOI":"10.1016\/B978-0-12-262503-9.50025-6"},{"key":"2021111418470262000_11.17.2153.6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/dna.1988.7.261","article-title":"p1B15: A cDNA clone of the rat mRNA encoding cyclophilin.","volume":"1","author":"Danielson","year":"1988","journal-title":"DNA"},{"key":"2021111418470262000_11.17.2153.7","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90531-3"},{"key":"2021111418470262000_11.17.2153.8","doi-asserted-by":"publisher","DOI":"10.1038\/378406a0"},{"key":"2021111418470262000_11.17.2153.9","unstructured":"Freeman M.E. (1994) The neuroendocrine control of the ovarian cycle of the rat. in The physiology of reproduction, eds Knobil E. Neill J.D. (Raven Press, New York, NY), pp 613\u2013658."},{"key":"2021111418470262000_11.17.2153.10","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.14.1654"},{"key":"2021111418470262000_11.17.2153.11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90519-2"},{"key":"2021111418470262000_11.17.2153.12","unstructured":"Greenwald G.E. Roy S.K. (1994) Follicular development and its control. in The physiology of reproduction, eds Knobil E. Neill J.D. (Raven Press, New York, NY), pp 629\u2013724."},{"key":"2021111418470262000_11.17.2153.13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.42.24965"},{"key":"2021111418470262000_11.17.2153.14","unstructured":"Johnson P. Williams S.C. (1994) CCAAT\/enhancer binding (C\/EBP) proteins. in Liver gene expression, eds Yaniv M. Tronche F. (R.G. Landes Company, Austin, TX), pp 231\u2013258."},{"key":"2021111418470262000_11.17.2153.15","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1002\/j.1460-2075.1993.tb05777.x","article-title":"The NF-M transcription factor is related to C\/EBP-\u03b2 and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells.","volume":"12","author":"Katz","year":"1993","journal-title":"EMBO J."},{"key":"2021111418470262000_11.17.2153.16","unstructured":"Knobil E. Neill J.D. (1994) The physiology of reproduction (Raven Press, New York, NY)."},{"key":"2021111418470262000_11.17.2153.17","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod55.5.984"},{"key":"2021111418470262000_11.17.2153.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5279.1219"},{"key":"2021111418470262000_11.17.2153.19","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1128\/MCB.17.4.2038","article-title":"The ability of C\/EBP beta but not C\/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain.","volume":"17","author":"Lee","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2021111418470262000_11.17.2153.20","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.4.533"},{"key":"2021111418470262000_11.17.2153.21","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/01.HYP.8.6.540","article-title":"Localization of preangiotensinogen messenger RNA in the rat brain.","volume":"8","author":"Lynch","year":"1986","journal-title":"Hypertension"},{"key":"2021111418470262000_11.17.2153.22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.28.16633"},{"key":"2021111418470262000_11.17.2153.23","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1182\/blood.V79.2.460.460","article-title":"Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6.","volume":"79","author":"Natsuka","year":"1992","journal-title":"Blood"},{"key":"2021111418470262000_11.17.2153.24","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1128\/MCB.17.7.3600","article-title":"CREB controls LAP\/C\/EBP\u03b2 transcription.","volume":"17","author":"Niehof","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2021111418470262000_11.17.2153.25","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.2.167"},{"key":"2021111418470262000_11.17.2153.26","doi-asserted-by":"publisher","DOI":"10.1210\/en.133.5.2327"},{"key":"2021111418470262000_11.17.2153.27","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0258"},{"key":"2021111418470262000_11.17.2153.28","unstructured":"Richards J.S. (1993) Gonadotropin-regulated gene expression in the ovary. in The ovary, eds Adashi E.Y. Leung P.C.K. (Raven Press, New York, NY), pp 93\u2013110."},{"key":"2021111418470262000_11.17.2153.29","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-15-6-725"},{"key":"2021111418470262000_11.17.2153.30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1322"},{"key":"2021111418470262000_11.17.2153.31","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1002\/j.1460-2075.1991.tb04948.x","article-title":"The CCAAT\/enhancer binding protein and its role in adipocyte differentiation: Evidence for direct involvement in terminal adipocyte development.","volume":"10","author":"Samuelsson","year":"1991","journal-title":"EMBO J."},{"key":"2021111418470262000_11.17.2153.32","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1182\/blood.V80.7.1725.1725","article-title":"A novel temporal expression pattern of three C\/EBP family members in differentiating myelomonocytic cells.","volume":"80","author":"Scott","year":"1992","journal-title":"Blood"},{"key":"2021111418470262000_11.17.2153.33","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1002\/j.1460-2075.1995.tb07185.x","article-title":"Lymphoproliferative disorder and imbalanced T-helper response in C\/EBP\u03b2-deficient mice.","volume":"14","author":"Screpanti","year":"1995","journal-title":"EMBO J."},{"key":"2021111418470262000_11.17.2153.34","doi-asserted-by":"publisher","DOI":"10.1038\/385525a0"},{"key":"2021111418470262000_11.17.2153.35","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1016\/S0021-9258(20)80630-9","article-title":"Transcriptional regulation of the rat prostaglandin endoperoxide synthase 2 gene in granulosa cells. Evidence for the role of a cis-acting C\/EBP beta promoter element.","volume":"268","author":"Sirois","year":"1993","journal-title":"J. Biol. Chem."},{"key":"2021111418470262000_11.17.2153.36","doi-asserted-by":"crossref","first-page":"11586","DOI":"10.1016\/S0021-9258(19)49951-1","article-title":"Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro.","volume":"267","author":"Sirois","year":"1992","journal-title":"J. Biol. Chem."},{"key":"2021111418470262000_11.17.2153.37","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1182\/blood.V88.4.1234.bloodjournal8841234","article-title":"PU.1 (Spi-1) and C\/EBP\u03b1 regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells.","volume":"88","author":"Smith","year":"1996","journal-title":"Blood"},{"key":"2021111418470262000_11.17.2153.38","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90499-O"},{"key":"2021111418470262000_11.17.2153.39","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1046\/j.1471-4159.1996.67041365.x","article-title":"Interleukin-6 induces expression of peripherin and cooperates with Trk receptor signaling to promote neuronal differentiation in PC12 cells.","volume":"67","author":"Sterneck","year":"1996","journal-title":"J. Neurochem."},{"key":"2021111418470262000_11.17.2153.40","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.11.2071"},{"key":"2021111418470262000_11.17.2153.41","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90418-2"},{"key":"2021111418470262000_11.17.2153.42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0076-6879(95)54028-8","article-title":"Oncogene techniques: In situ hybridization.","volume":"254","author":"Tessarollo","year":"1995","journal-title":"Methods Enzymol."},{"key":"2021111418470262000_11.17.2153.43","doi-asserted-by":"publisher","DOI":"10.1007\/BF00318679"},{"key":"2021111418470262000_11.17.2153.44","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(95)00232-4"},{"key":"2021111418470262000_11.17.2153.45","doi-asserted-by":"publisher","DOI":"10.1126\/science.7652557"},{"key":"2021111418470262000_11.17.2153.46","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.9.1553"},{"key":"2021111418470262000_11.17.2153.47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.31315"},{"key":"2021111418470262000_11.17.2153.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.2.569"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.11.17.2153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T03:07:54Z","timestamp":1636945674000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.11.17.2153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,9,1]]},"references-count":48,"journal-issue":{"issue":"17","published-print":{"date-parts":[[1997,9,1]]}},"alternative-id":["10.1101\/gad.11.17.2153"],"URL":"https:\/\/doi.org\/10.1101\/gad.11.17.2153","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,9,1]]}}}