Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase

The effects of testosterone on early atherogenesis and the role of aromatas e, an enzyme that converts testosterone to estrogens, were assessed in low density lipoprotein receptor-deficient male mice fed a Western diet, Castra tion of male mice increased the extent of fatty streak lesion formation in the aortic origin compared with testes-intact animals, Administration of an astrazole, a selective aromatase inhibitor, to testes-intact males increase d lesion formation to the same extent as that observed with orchidectomized animals, Testosterone supplementation of orchidectomized animals reduced l esion formation when compared with orchidectomized animals receiving the pl acebo. This attenuating effect of testosterone was not observed when the an imals were treated simultaneously with the aromatase inhibitor, The benefic ial effects of testosterone on early atherogenesis were not explained by ch anges in lipid levels. Estradiol administration to orchidectomized males at tenuated lesion formation to the same extent as testosterone administration . Aromatase was expressed in the aorta of these animals as assessed by reve rse transcription-PCR and immunohistochemistry. These results indicate that testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall.