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Androgens exert beneficial effects on the cardiovascular system and testosterone (TES) replacement therapy improves cardiometabolic risk factors. However, TES is contraindicated in patients with prostate cancer due to its proliferative effects on prostatic tumor cells. Additionally, TES and its reduced metabolites 5\u03b1- and 5\u03b2-dihydrotestosterone (5\u03b1-DHT and 5\u03b2-DHT) exert vasodilatory effects. Since androgen levels decrease during aging and 5\u03b2-DHT lacks genomic effects, this study is focused on analyzing its effect on vasodilator function and the proliferation rate of prostatic tumor and vascular smooth muscle cells. To study the vascular function, mesenteric arteries from aged-orchidectomized Sprague-Dawley rats were used. Mesenteric segments were divided into one control (without treatment) and three groups with the androgens (10 nM, 30 min) to analyze: acetylcholine- and sodium nitroprusside-induced responses and nitric oxide and superoxide anion production. To analyze cell proliferation, the effect of androgens on cell viability was determined. The results showed that 5\u03b2-DHT improves vasodilator function in arteries from aged-orchidectomized rats and induces antioxidant action, while the proliferation rate of the androgen-dependent prostatic tumor cells remains unaltered. These results make 5\u03b2-DHT a promising therapeutic agent for the treatment of cardiovascular pathologies.<\/jats:p>","DOI":"10.1371\/journal.pone.0312080","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T17:27:51Z","timestamp":1729704471000},"page":"e0312080","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of 5\u03b2-dihydrotestosterone on vasodilator function and on cell proliferation"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5714-8399","authenticated-orcid":true,"given":"David","family":"S\u00e1nchez-Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritz","family":"Eguibar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6596-9600","authenticated-orcid":true,"given":"\u00c1ngel M.","family":"Cuesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Albi\u00f1ana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soline","family":"Rogers-Ezewuike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0556-3035","authenticated-orcid":true,"given":"Juan A.","family":"G\u00f3mez-Rivas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Salda\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa M.","family":"Botella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4670-7146","authenticated-orcid":true,"given":"Mercedes","family":"Ferrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"pone.0312080.ref001","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.niox.2005.02.003","article-title":"Androgen deprivation increases neuronal nitric oxide metabolism and its vasodilator effect in rat mesenteric arteries","volume":"12","author":"M del C Mart\u00edn","year":"2005","journal-title":"Nitric Oxide"},{"key":"pone.0312080.ref002","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1677\/joe.1.06887","article-title":"Orchidectomy increases expression and activity of Cu\/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability","volume":"190","author":"J Blanco-Rivero","year":"2006","journal-title":"Journal of Endocrinology"},{"key":"pone.0312080.ref003","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1093\/cvr\/cvm059","article-title":"Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta","volume":"77","author":"A Martorell","year":"2008","journal-title":"Cardiovasc Res"},{"key":"pone.0312080.ref004","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/CS20120700","article-title":"Testosterone and \u03b2-oestradiol prevent inward remodelling of rat small mesenteric arteries: role of NO and transglutaminase","volume":"124","author":"L del Campo","year":"2013","journal-title":"Clin Sci (Lond)"},{"key":"pone.0312080.ref005","doi-asserted-by":"crossref","first-page":"e102523","DOI":"10.1371\/journal.pone.0102523","article-title":"Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. 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Perusqu\u00eda","year":"2003","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"pone.0312080.ref017","doi-asserted-by":"crossref","first-page":"H1301","DOI":"10.1152\/ajpheart.00753.2009","article-title":"Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites","volume":"298","author":"M Perusqu\u00eda","year":"2010","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"pone.0312080.ref018","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.vph.2012.01.008","article-title":"Regional differences in the vasorelaxing effects of testosterone and its 5-reduced metabolites in the canine vasculature","volume":"56","author":"M Perusqu\u00eda","year":"2012","journal-title":"Vascul Pharmacol"},{"key":"pone.0312080.ref019","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jsbmb.2017.11.001","article-title":"Antihypertensive responses of vasoactive androgens in an in vivo experimental model of preeclampsia","volume":"178","author":"M Perusqu\u00eda","year":"2018","journal-title":"J Steroid Biochem Mol Biol"},{"key":"pone.0312080.ref020","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1080\/07435800.2018.1448868","article-title":"Vasoactive androgens: Vasorelaxing effects and their potential regulation of blood pressure","volume":"43","author":"L Isidoro","year":"2018","journal-title":"Endocr Res"},{"key":"pone.0312080.ref021","first-page":"16","article-title":"Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation","author":"L Isidoro-Garc\u00eda","year":"2021","journal-title":"PLoS One"},{"issue":"2","key":"pone.0312080.ref022","doi-asserted-by":"crossref","first-page":"R189","DOI":"10.1152\/ajpregu.00110.2015","article-title":"Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent","volume":"309","author":"M Perusqu\u00eda","year":"2015","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"pone.0312080.ref023","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jsbmb.2016.11.016","article-title":"Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats","volume":"167","author":"M Perusqu\u00eda","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"key":"pone.0312080.ref024","first-page":"196","article-title":"Intracrinology-revisited and prostate cancer","author":"TM Penning","year":"2020","journal-title":"J Steroid Biochem Mol Biol"},{"key":"pone.0312080.ref025","doi-asserted-by":"crossref","first-page":"174251","DOI":"10.1016\/j.ejphar.2021.174251","article-title":"Kaempferol inhibits benign prostatic hyperplasia by resisting the action of androgen","volume":"907","author":"X Wang","year":"2021","journal-title":"Eur J Pharmacol"},{"key":"pone.0312080.ref026","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1016\/j.jacc.2022.11.005","article-title":"The Global Burden of Cardiovascular Diseases and Risk: A Compass for Future Health","volume":"80","author":"M Vaduganathan","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"pone.0312080.ref027","unstructured":"M Steverson. Ageing and Health. In: World Health Organization [Internet]. 1 Oct 2022 [cited 13 Mar 2024]. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/ageing-and-health"},{"issue":"4","key":"pone.0312080.ref028","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1042\/cs0990277","article-title":"Balfag\u00f3n G. Role of protein kinase C in electrical-stimulation-induced neuronal nitric oxide release in mesenteric arteries from hypertensive rats","volume":"99","author":"J Mar\u00edn","year":"2000","journal-title":"Clin Sci"},{"key":"pone.0312080.ref029","first-page":"6","volume-title":"Basic and Clinical Endocrinology Up-to-Date","author":"M Ferrer","year":"2011"},{"key":"pone.0312080.ref030","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1161\/HYPERTENSIONAHA.110.162719","article-title":"Sphingosine-1-Phosphate-Induced Inflammation Involves Receptor Tyrosine Kinase Transactivation in Vascular Cells","volume":"57","author":"A Yogi","year":"2011","journal-title":"Hypertension"},{"key":"pone.0312080.ref031","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0006-8993(71)90370-2","article-title":"Contractile response and amine receptor mechanisms in isolated middle cerebral artery of the cat","volume":"27","author":"KC Nielsen","year":"1971","journal-title":"Brain Res"},{"issue":"2","key":"pone.0312080.ref032","doi-asserted-by":"crossref","first-page":"R233","DOI":"10.1152\/ajpregu.00338.2003","article-title":"Gender, sex hormones, and vascular tone","volume":"286","author":"JM Orshal","year":"2004","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"pone.0312080.ref033","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cardiores.2004.12.027","article-title":"Endothelial aging","volume":"66","author":"RP Brandes","year":"2005","journal-title":"Cardiovasc Res"},{"key":"pone.0312080.ref034","first-page":"2014","article-title":"The Role of Oxidative Stress and Inflammation in Cardiovascular Aging","author":"J Wu","year":"2014","journal-title":"Biomed Res Int"},{"key":"pone.0312080.ref035","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1113\/JP270597","article-title":"Arterial structure and function in vascular ageing: are you as old as your arteries?","volume":"594","author":"DHJ Thijssen","year":"2016","journal-title":"J Physiol"},{"key":"pone.0312080.ref036","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCRESAHA.118.311378","article-title":"Mechanisms of Vascular Aging","volume":"123","author":"Z Ungvari","year":"2018","journal-title":"Circ Res"},{"key":"pone.0312080.ref037","first-page":"16","article-title":"Revisiting the role of testosterone: Are we missing something?","volume":"19","author":"V Tyagi","year":"2017","journal-title":"Rev Urol"},{"key":"pone.0312080.ref038","doi-asserted-by":"crossref","DOI":"10.1097\/00004872-199307000-00003","article-title":"Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension","volume":"11","author":"GB Phillips","year":"1993","journal-title":"J Hypertens"},{"key":"pone.0312080.ref039","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1210\/er.2003-0005","article-title":"Androgens and Cardiovascular Disease","volume":"24","author":"PY Liu","year":"2003","journal-title":"Endocr Rev"},{"key":"pone.0312080.ref040","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1111\/andr.12876","article-title":"Late-onset hypogonadism: Reductio ad absurdum of the cardiovascular risk-benefit of testosterone replacement therapy","volume":"8","author":"F Sesti","year":"2020","journal-title":"Andrology"},{"key":"pone.0312080.ref041","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000089791","article-title":"Orchidectomy modulates alpha2-adrenoceptor reactivity in rat mesenteric artery through increased thromboxane A2 formation","volume":"43","author":"J Blanco-Rivero","year":"2006","journal-title":"J Vasc Res"},{"key":"pone.0312080.ref042","doi-asserted-by":"crossref","first-page":"e0142039","DOI":"10.1371\/journal.pone.0142039","article-title":"Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats","volume":"10","author":"DM Villalpando","year":"2015","journal-title":"PLoS One"},{"key":"pone.0312080.ref043","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/s12020-019-01978-x","article-title":"Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens","volume":"65","author":"M Perusqu\u00eda","year":"2019","journal-title":"Endocrine"},{"key":"pone.0312080.ref044","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0168841","article-title":"Docosahexaenoic acid supplemented diet influences the orchidectomy-induced vascular dysfunction in rat mesenteric arteries","volume":"12","author":"DM Villalpando","year":"2017","journal-title":"PLoS One"},{"key":"pone.0312080.ref045","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23073535","article-title":"The Role of Testosterone in the Elderly: What Do We Know?","volume":"23","author":"B Barone","year":"2022","journal-title":"Int J Mol Sci"},{"key":"pone.0312080.ref046","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13048","article-title":"The role of lipid metabolism in aging, lifespan regulation, and age\u2010related disease","volume":"18","author":"AA Johnson","year":"2019","journal-title":"Aging Cell"},{"key":"pone.0312080.ref047","doi-asserted-by":"crossref","first-page":"1900098","DOI":"10.1002\/ejlt.201900098","article-title":"Conjugated Linoleic Acid Supplemented Diet Influences Serum Markers in Orchidectomized Sprague-Dawley Rats","volume":"122","author":"MM Rojas","year":"2020","journal-title":"European Journal of Lipid Science and Technology"},{"key":"pone.0312080.ref048","doi-asserted-by":"crossref","first-page":"C254","DOI":"10.1152\/ajpcell.00315.2016","article-title":"Nitric oxide: what\u2019s new to NO?","volume":"312","author":"K Ghimire","year":"2017","journal-title":"Am J Physiol Cell Physiol"},{"issue":"12","key":"pone.0312080.ref049","doi-asserted-by":"crossref","first-page":"4927","DOI":"10.1210\/en.2011-1424","article-title":"Endothelial dysfunction in a rat model of PCOS: evidence of increased vasoconstrictor prostanoid activity","volume":"152","author":"JL Keller","year":"2011","journal-title":"Endocrinology"},{"key":"pone.0312080.ref050","doi-asserted-by":"crossref","DOI":"10.1186\/s13293-024-00586-3","article-title":"Dihydrotestosterone induces arterial stiffening in female mice","volume":"15","author":"AC Horton","year":"2024","journal-title":"Biol Sex Differ"},{"key":"pone.0312080.ref051","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1096\/fasebj.3.9.2545495","article-title":"Endothelium-derived relaxing and contracting factors","volume":"3","author":"RF Furchgott","year":"1989","journal-title":"The FASEB Journal"},{"key":"pone.0312080.ref052","unstructured":"S\u00e1nchez D, Mateo A, Rodr\u00edguez P, Mart\u00ednez B, Eguibar A, G\u00f3mez-Rivas J, et al. Effect of androgens on vasomotor responses in arteries with vascular dysfunction. Role of nitric oxide. Vasculature in Disease I. Oakland: 22nd International Vascular Biology Meeting; 2022."},{"key":"pone.0312080.ref053","doi-asserted-by":"crossref","first-page":"H1829","DOI":"10.1152\/ajpheart.00230.2009","article-title":"eNOS uncoupling and endothelial dysfunction in aged vessels","volume":"297","author":"Y-M Yang","year":"2009","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"pone.0312080.ref054","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/hr.2015.114","article-title":"Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling","volume":"39","author":"S Battault","year":"2016","journal-title":"Hypertension Research"},{"key":"pone.0312080.ref055","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/nrd2222","article-title":"Peroxynitrite: biochemistry, pathophysiology and development of therapeutics","volume":"6","author":"C Szab\u00f3","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"pone.0312080.ref056","author":"KL Hensley","year":"2003","journal-title":"Nitrite Determination by Colorimetric and Fluorometric Griess Diazotization Assays"},{"key":"pone.0312080.ref057","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1023\/B:JANC.0000043920.77446.d7","article-title":"The 125th Anniversary of the Griess Reagent","volume":"59","author":"VM Ivanov","year":"2004","journal-title":"Journal of Analytical Chemistry"},{"key":"pone.0312080.ref058","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0039-128X(00)00183-5","article-title":"In vitro effects of different steroid hormones on superoxide anion production of human neutrophil granulocytes","volume":"65","author":"G B\u00e9k\u00e9si","year":"2000","journal-title":"Steroids"},{"key":"pone.0312080.ref059","doi-asserted-by":"crossref","first-page":"E1067","DOI":"10.1152\/ajpendo.00173.2002","article-title":"Effect of treatment of diabetic rats with dehydroepiandrosterone on vascular and neural function","volume":"283","author":"MA Yorek","year":"2002","journal-title":"American Journal of Physiology-Endocrinology and Metabolism"},{"key":"pone.0312080.ref060","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.1016\/S0024-3205(01)01089-X","article-title":"Influence of 5\u03b1- and 5\u03b2-reduced progestins on the contractility of isolated human myometrium at term","volume":"68","author":"M Perusqu\u00eda","year":"2001","journal-title":"Life Sci"},{"key":"pone.0312080.ref061","doi-asserted-by":"crossref","DOI":"10.1186\/s13293-024-00624-0","article-title":"Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement","volume":"15","author":"A Sakamuri","year":"2024","journal-title":"Biol Sex Differ"},{"key":"pone.0312080.ref062","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.freeradbiomed.2016.04.198","article-title":"Mitochondrial ROS regulation of proliferating cells","volume":"100","author":"L Diebold","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"pone.0312080.ref063","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.steroids.2012.05.008","article-title":"Cellular actions of testosterone in vascular cells: Mechanism independent of aromatization to estradiol","volume":"77","author":"AE Campelo","year":"2012","journal-title":"Steroids"},{"key":"pone.0312080.ref064","doi-asserted-by":"crossref","first-page":"704.e15","DOI":"10.1016\/j.urology.2014.11.026","article-title":"Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia","volume":"85","author":"PI Adolfsson","year":"2015","journal-title":"Urology"},{"key":"pone.0312080.ref065","doi-asserted-by":"crossref","first-page":"C805","DOI":"10.1152\/ajpcell.00127.2007","article-title":"PKC\u03b4 mediates anti-proliferative, pro-apoptic effects of testosterone on coronary smooth muscle","volume":"293","author":"DK 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