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Androgen receptor-dependent and independent atheroprotection by testosterone in male mice
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
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2010 (Engelska)Ingår i: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 151, nr 11, s. 5428-5437Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P < 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P < 0.001) and ARKO mice (by 24%, P < 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P < 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P < 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

Ort, förlag, år, upplaga, sidor
Endocrine Society , 2010. Vol. 151, nr 11, s. 5428-5437
Nationell ämneskategori
Annan medicinsk grundvetenskap
Forskningsämne
Medicin
Identifikatorer
URN: urn:nbn:se:his:diva-11378DOI: 10.1210/en.2010-0663ISI: 000283231700036PubMedID: 20861231Scopus ID: 2-s2.0-78049516208OAI: oai:DiVA.org:his-11378DiVA, id: diva2:847226
Tillgänglig från: 2015-08-19 Skapad: 2015-08-19 Senast uppdaterad: 2018-01-11Bibliografiskt granskad

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