title: Reactive oxygen species: players in the cardiovascular effects of testosterone.
abstract: Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed.
authors.affiliation: University of São Paulo, Ribeirao Preto Medical School, Ribeirao Preto, São Paulo, Brazil; rtostes@usp.br.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Tostes
authors.affiliation: University of São Paulo, Ribeirao Preto Medical School, Ribeirao Preto, São Paulo, Brazil;
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Carneiro
authors.affiliation: University of São Paulo, Institute of Biomedical Sciences, São Paulo, Brazil; and.
authors.forename: Maria Helena C
authors.initials: MH
authors.lastname: Carvalho
authors.affiliation: University of Mississippi Medical Center, Women's Health Research Center, Jackson, Mississippi.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
mesh_terms: D000367:Age Factors; D000818:Animals; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002319:Cardiovascular System / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction; D013739:Testosterone / Q000009:adverse effects / Q000172:deficiency / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013739:Testosterone
keywords: antioxidant; cardiovascular; prooxidant