{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:19:44Z","timestamp":1767831584100,"version":"3.49.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Murine epididymal retinoic acid-binding protein [or lipocalin 5 (Lcn5)] is synthesized and secreted by the principal cells of the mouse middle\/distal caput epididymidis. A 5-kb promoter fragment of the Lcn5 gene can dictate androgen-dependent and epididymis region-specific gene expression in transgenic mice. Here, we reported that the 1.8-kb Lcn5 promoter confers epididymis region-specific gene expression in transgenic mice. To decipher the mechanism that directs transcription, 14 chimeric constructs that sequentially removed 100 bp of 1.8-kb Lcn5 promoter were generated and transfected into epididymal cells and nonepididymal cells. Transient transfection analysis revealed that 1.3 kb promoter fragment gave the strongest response to androgens. Between the 1.2-kb to 1.3-kb region, two androgen receptor (AR) binding sites were identified. Adjacent to AR binding sites, a Foxa2 [Fox (Forkhead box) subclass A] binding site was confirmed by gel shift assay. Similar Foxa binding sites were also found on the promoters of human and rat Lcn5, indicating the Foxa binding site is conserved among species. We previously reported that among the three members of Foxa family, Foxa1 and Foxa3 were absent in the epididymis whereas Foxa2 was detected in epididymal principal cells. Here, we report that Foxa2 displays a region-specific expression pattern along the epididymis: no staining observed in initial segment, light staining in proximal caput, gradiently heavier staining in middle and distal caput, and strongest staining in corpus and cauda, regions with little or no expression of Lcn5. In transient transfection experiments, Foxa2 expression inhibits AR induction of the Lcn5 promoter, which is consistent with the lack of expression of Lcn5 in the corpus and cauda. We conclude that Foxa2 functions as a repressor that restricts AR regulation of Lcn5 to a segment-specific pattern in the epididymis.<\/jats:p>","DOI":"10.1210\/me.2006-0008","type":"journal-article","created":{"date-parts":[[2006,6,2]],"date-time":"2006-06-02T00:48:52Z","timestamp":1149209332000},"page":"2418-2431","source":"Crossref","is-referenced-by-count":25,"title":["The Role of Forkhead Box A2 to Restrict Androgen-Regulated Gene Expression of Lipocalin 5 in the Mouse Epididymis"],"prefix":"10.1210","volume":"20","author":[{"given":"Xiuping","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kichiya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"},{"name":"Center for Reproductive Biology Research (K.S., M.-C.O.-C.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparna","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renjie","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Claire","family":"Orgebin-Crist","sequence":"additional","affiliation":[{"name":"Center for Reproductive Biology Research (K.S., M.-C.O.-C.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Matusik","sequence":"additional","affiliation":[{"name":"Department of Urologic Surgery (X.Y., K.S., Y.W., A.G., R.J., R.M.), Nashville, Tennessee 37232"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071614051690800_R1","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1210\/endo.139.6.6074","article-title":"Molecular cloning and hormonal regulation of a murine epididymal retinoic acid-binding protein mRNA.","volume":"139","author":"Lareyre","year":"1998","journal-title":"Endocrinology"},{"key":"2020071614051690800_R2","first-page":"59","article-title":"Structure and putative function of a murine epididymal retinoic acid-binding protein (mE-RABP).","volume":"53","author":"Lareyre","year":"1998","journal-title":"J Reprod Fertil Suppl"},{"key":"2020071614051690800_R3","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1095\/biolreprod46.5.767","article-title":"The 18-kDa mouse epididymal protein (MEP 10) binds retinoic acid.","volume":"46","author":"Rankin","year":"1992","journal-title":"Biol Reprod"},{"key":"2020071614051690800_R4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0167-4838(00)00156-4","article-title":"Epididymal retinoic acid-binding protein.","volume":"1482","author":"Ong","year":"2000","journal-title":"Biochim Biophys Acta"},{"key":"2020071614051690800_R5","first-page":"47","article-title":"Testicular regulation of epididymal gene expression.","volume":"53","author":"Hinton","year":"1998","journal-title":"J Reprod Fertil Suppl"},{"key":"2020071614051690800_R6","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0167-4838(00)00164-3","article-title":"Immunocalins: a lipocalin subfamily that modulates immune and inflammatory 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dwarfism.","volume":"384","author":"Sornson","year":"1996","journal-title":"Nature"},{"key":"2020071614051690800_R34","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0959-437X(98)80008-7","article-title":"Muscle differentiation: more complexity to the network of myogenic regulators.","volume":"8","author":"Arnold","year":"1998","journal-title":"Curr Opin Genet Dev"},{"key":"2020071614051690800_R35","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1016\/S0021-9258(17)42053-9","article-title":"Cloning and identification of testis-specific transcription elongation factor S-II.","volume":"269","author":"Xu","year":"1994","journal-title":"J Biol Chem"},{"key":"2020071614051690800_R36","doi-asserted-by":"crossref","first-page":"16365","DOI":"10.1016\/S0021-9258(18)42011-X","article-title":"Mammary gland-specific nuclear factor is present in lactating rodent and bovine mammary tissue and composed of a single polypeptide of 89 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