title: Testosterone metabolites mediate its effects on myocardial damage induced by ischemia/reperfusion in male Wistar rats.
abstract: The role of testosterone in cardiovascular (CV) homeostasis is in controversy, and the exact effects of testosterone on the cardiovascular system remain poorly understood. Testosterone is metabolized by aromatase into 17β-estradiol and by 5α-reductase into dihydrotestosterone (DHT). Thus, identification of these metabolites in the heart may help to explain the controversy regarding the cardiovascular effects of testosterone. We analyzed the expression patterns of these testosterone-metabolizing enzymes and assessed the effect of its enzymatic activity inhibition on ischemia (40 min)/reperfusion (4h, I/R) via the left anterior descendent coronary artery in intact and gonadectomized male rats. Myocardial damage was measured as percentage of infarcted area vs. area at risk. Aromatase and 5α-reductase protein expression was found in the left ventricle of intact and orchidectomized rats. Exogenous testosterone had no effect on I/R induced myocardial damage in intact male rats, meanwhile exogenous testosterone protects against I/R injury in orchidectomized rats. However, enzymatic inhibition of aromatase increased myocardial damage in the presence of testosterone, while enzymatic inhibition of 5α-reductase significantly decreased the level of myocardial damage. Our results also showed that sub-chronic inhibition of 5α-reductase resulted in myocardial protection in both groups. Furthermore, in orchidectomized and intact male rats IV treatment with DHT induces a significant increase in the myocardial damage induced by I/R. Thus, the effect of testosterone on cardiovascular pathophysiology could be related, at least in part to changes in the balance of testosterone 5α-reduction and aromatization.
authors.affiliation: Seccion de Estudios de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, Mexico.
authors.forename: Ivan
authors.initials: I
authors.lastname: Rubio-Gayosso
authors.forename: Israel
authors.initials: I
authors.lastname: Ramirez-Sanchez
authors.forename: Israel
authors.initials: I
authors.lastname: Ita-Islas
authors.forename: Pilar
authors.initials: P
authors.lastname: Ortiz-Vilchis
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gutierrez-Salmean
authors.forename: Alejandra
authors.initials: A
authors.lastname: Meaney
authors.forename: Icela
authors.initials: I
authors.lastname: Palma
authors.forename: Ivonne
authors.initials: I
authors.lastname: Olivares
authors.forename: Ruben
authors.initials: R
authors.lastname: Garcia
authors.forename: Eduardo
authors.initials: E
authors.lastname: Meaney
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ceballos
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology; D000735:Androstenedione / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D058891:5-alpha Reductase Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D018120:Finasteride; D001141:Aromatase; D042944:Cholestenone 5 alpha-Reductase