{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:40:29Z","timestamp":1790995229844,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non\u2010genomic pathway\u00a0has been reported; however, the in vitro modulating effects of\u00a0T\u00a0on human corpus cavernosum (HCC) have not been studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To compare the effects of various concentrations of T on nitric oxide (NO)\u2010dependent and nitric oxide\u2010independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO\/cyclic guanosine monophosphate (cGMP) pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n\u00a0=\u00a09). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150\u00a0ng\/dL), eugonadal (400\u00a0ng\/dL), and hypergonadal (600\u00a0ng\/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite\/nitrate (NOx) assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil\u2010induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals an important role of short\u2010term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.12866","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T05:10:07Z","timestamp":1594876207000},"page":"1824-1833","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum"],"prefix":"10.1111","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1730-7282","authenticated-orcid":false,"given":"Serap","family":"Gur","sequence":"first","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"},{"name":"Department of Pharmacology Faculty of Pharmacy Ankara University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laith","family":"Alzweri","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"},{"name":"Division of Urology, Department of Surgery University of Texas Medical Branch Galveston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Yilmaz\u2010Oral","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy Cukurova University Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecem","family":"Kaya\u2010Sezginer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy Ankara University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim B","family":"Abdel\u2010Mageed","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Dick","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh C.","family":"Sikka","sequence":"additional","affiliation":[{"name":"Department of Urology Tulane University Health Sciences Center New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cetin","family":"Volkan Oztekin","sequence":"additional","affiliation":[{"name":"Department of Urology Faculty of Medicine University of Kyrenia Turkish Republic of North Cyprus Girne, Mersin 10 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-959X","authenticated-orcid":false,"given":"Wayne J. 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