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Failure of the exposure to 5\u03b1\u2010dihydrotestosterone (<jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content>) causes a hypoplastic penile size and urethral abnormality. The main pathology of hypospadias is defective urethral closure on the ventral side of the penis. Hormone\u2010dependent genes are suggested as the causative factors. However, the detailed mechanisms of <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content> functions on urethral tube formation remain unknown. Androgen is both a positive and negative regulator of cell proliferation. The roles of locally converted <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content> in cell proliferation at the periurethral mesenchyme have not been elucidated. We revealed the expression pattern of 5\u03b1\u2010reductase type 2 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> (<jats:italic>Srd5a2<\/jats:italic>) and local <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content> distribution by direct measurement in this study. We also analyzed periurethral mesenchymal cell proliferation status using systematic three\u2010dimensional (3D) reconstruction analyses. A prominent <jats:italic>Srd5a2<\/jats:italic> expression and localized <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content> distribution on the ventral side of the genital tubercle were detected. Cell proliferation was reduced in this mesenchymal region during urethral formation. The current results suggest the presence of the possible negative regulation of cell proliferation by <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content>. Moreover, cell proliferation related to urethral tube formation was revealed to be <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content> dose dependent. These data are expected to contribute to the understanding of the mode of regulation of cell proliferation related to urethral tube formation by <jats:styled-content style=\"fixed-case\">DHT<\/jats:styled-content>. These findings may also offer insight into the understanding of human hypospadias and related hormone\u2010dependent factors.<\/jats:p>","DOI":"10.1111\/andr.12241","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T13:02:57Z","timestamp":1475845377000},"page":"146-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["5\u03b1\u2010Dihydrotestosterone negatively regulates cell proliferation of the periurethral ventral mesenchyme during urethral tube formation in the murine male genital tubercle"],"prefix":"10.1111","volume":"5","author":[{"given":"H.","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Developmental Genetics Institute of Advanced Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of 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