title: Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway.
abstract: The aim of the present study was to investigate the effect of testosterone on the modulation of cellular events associated with vascular homeostasis. In rat aortic strips, 5-20 min treatment with physiological concentrations of testosterone significantly increased nitric oxide (NO) production. The rapid action of the steroid was suppressed by the presence of an androgen receptor antagonist (flutamide). We obtained evidence that the enhancement in NO synthesis was dependent on the influx of calcium from extracellular medium, because in the presence of a calcium channel blocker (verapamil) the effect of testosterone was reduced. Using endothelial cell (EC) cultures, we demonstrated that androgen directly acts at the endothelial level. Chelerythrine or PD98059 compound completely suppressed the increase in NO production, suggesting that the mechanism of action of the steroid involves protein kinase C and mitogen-activated protein kinase pathways. It is known that endothelial NO released into the vascular lumen serves as an inhibitor of platelet activation and aggregation. We showed that testosterone inhibited platelet aggregation and this effect was dependent on endothelial NO synthesis. Indeed, the enhancement of NO production elicited by androgen was associated with EC growth. The steroid significantly increased DNA synthesis after 24 h of treatment, and this mitogenic action was blunted in the presence of NO synthase inhibitor N-nitro-l-arginine methyl ester. In summary, testosterone modulates vascular EC growth and platelet aggregation through its direct action on endothelial NO production.
authors.affiliation: Cátedra de Bioquímica Clínica II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, Bahía Blanca, Argentina.
authors.forename: Adrián E
authors.initials: AE
authors.lastname: Campelo
authors.forename: Pablo H
authors.initials: PH
authors.lastname: Cutini
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Massheimer
mesh_terms: D000728:Androgens / Q000502:physiology*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013739:Testosterone / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000728:Androgens; D053119:Benzophenanthridines; D002121:Calcium Channel Blockers; D005419:Flavonoids; D009569:Nitric Oxide; D013739:Testosterone; D014700:Verapamil; C016299:chelerythrine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one