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Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the penis in <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> are not known. Given the critical role of androgens in erection physiology and <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> synthase (<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5 expression, we hypothesized that testosterone replacement to eugonadal testosterone levels reduces priapism by reversing impaired endothelial (e)<jats:styled-content style=\"fixed-case\">NOS<\/jats:styled-content> activity and molecular abnormalities involving <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5. Adult male transgenic Berkeley sickle cell (Sickle) and wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) mice were implanted with testosterone pellets, which release 1.2\u00a0\u03bcg testosterone\/day for 21\u00a0days, or vehicle. After 21\u00a0days, animals underwent erectile function assessment followed by collection of blood for serum testosterone measurements, penes for molecular analysis, and seminal vesicles as testosterone\u2010responsive tissue. Serum testosterone levels were measured by radioimmunoassay; protein expressions of <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5, \u03b1\u2010smooth muscle actin, <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content>, and phosphorylation of <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5 at Ser\u201092, <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> at Ser\u20101177, neuronal (n) NOS at Ser\u20101412, and Akt at Ser\u2010473 were measured by Western blot in penile tissue. Testosterone treatment reversed downregulated serum testosterone levels and increased (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) the weight of seminal vesicles in Sickle mice to levels comparable to that of <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice, indicating restored testosterone levels in Sickle mice. Testosterone treatment reduced (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) prolonged detumescence in Sickle mice and normalized downregulated P\u2010<jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5 (Ser\u201092), <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5, P\u2010<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> (Ser\u20101177), and P\u2010Akt (Ser\u2010473) protein expressions in the Sickle mouse penis. Testosterone treatment did not affect P\u2010<jats:styled-content style=\"fixed-case\">nNOS<\/jats:styled-content> (Ser\u20101412), <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> nNOS<\/jats:styled-content>, or \u03b1\u2010smooth muscle actin protein expressions in the Sickle mouse penis. In conclusion, in the mouse model of human <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>, increasing testosterone to eugonadal levels reduced priapic activity and reversed impaired Akt\/<jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content> activity and <jats:styled-content style=\"fixed-case\">PDE<\/jats:styled-content>5 protein expression in the penis.<\/jats:p>","DOI":"10.1111\/andr.12442","type":"journal-article","created":{"date-parts":[[2017,11,16]],"date-time":"2017-11-16T23:00:37Z","timestamp":1510873237000},"page":"184-191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Testosterone replacement in transgenic sickle cell mice controls priapic activity and upregulates PDE5 expression and eNOS activity in the penis"],"prefix":"10.1111","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0437-980X","authenticated-orcid":false,"given":"B.","family":"Musicki","sequence":"first","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Karakus","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Akakpo","sequence":"additional","affiliation":[{"name":"The James Buchanan Brady Urological Institute and Department of Urology The Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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