Cellular actions of testosterone in vascular cells: mechanism independent of aromatization to estradiol.
In this work we investigated the role of testosterone on cellular processes involved in vascular disease, and whether these effects depend on its local conversion to estradiol. Cultures of rat aortic endothelial and smooth muscle cells in vitro treated with physiological concentrations of testosterone were employed. Testosterone rapidly increased endothelial nitric oxide production. To evaluate whether this non genomic action was dependent on testosterone aromatization we used an aromatase inhibitor. Anastrozole compound did not modify the fast increase in nitric oxide production elicited by testosterone. The hormonal effect was completely blocked by an androgen receptor antagonist (flutamide); meanwhile it wasn't modified by the presence of an estrogen receptor antagonist (ICI182780).The possibility of intracellular estradiol synthesis was ruled out when no differences were found in estradiol measurements performed in culture incubation medium from control and testosterone treated cells. The 5α-reductase inhibitor finasteride partially suppressed the enhancement in nitric oxide production, suggesting that the effect of testosterone was partially due to dihydrotestosterone conversion. Testosterone stimulated muscle cell proliferation independent of local conversion to estradiol. When cellular events that play key roles in vascular disease development were analyzed, testosterone prevented monocyte adhesion to endothelial cells induced by a proinflammatory stimulus (bacterial lipopolysaccharides), and prompted muscle cell migration in presence of a cell motility inducer. In summary, testosterone modulates vascular behavior through its direct action on vascular cells independent of aromatization to estradiol. The cellular actions exhibited by the steroid varied whether cells were under basal or inflammatory conditions.
Cátedra de Bioquímica Clínica II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina.
Adrián E
AE
Campelo
Pablo H
PH
Cutini
Virginia L
VL
Massheimer
D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology; D000077384:Anastrozole; D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D018120:Finasteride / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D000077267:Fulvestrant; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000819:agonists* / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
D058891:5-alpha Reductase Inhibitors; D000726:Androgen Antagonists; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D014230:Triazoles; D000077267:Fulvestrant; D000077384:Anastrozole; D009569:Nitric Oxide; D013739:Testosterone; D004958:Estradiol; D018120:Finasteride; D005485:Flutamide