title: Androgen increases AT1a receptor expression in abdominal aortas to promote angiotensin II-induced AAAs in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Castration of male apolipoprotein E-deficient (apoE-/-) mice reduces angiotensin II (Ang II)-induced abdominal aorta aneurysms (AAAs) to that of female mice. The purpose of this study was to determine whether this reduction is attributable to androgen-mediated regulation of aortic Ang II type 1A receptors (AT1aR).
  
  
  RESULTS
  AT1aR mRNA abundance in the AAA-prone region of abdominal aortas was 8-fold greater compared to thoracic aortas of male but not female mice. AT1aR mRNA abundance decreased after castration in abdominal but not thoracic aortas of male mice. Dihydrotestosterone (DHT, 0.16 mg/d) administration to castrated male mice restored AT1aR mRNA abundance in abdominal aortas but had no effect in thoracic aortas. DHT also increased AT1aR mRNA abundance in abdominal aortas from female mice. Castrated male or female apoE-/- mice were administered DHT during infusion of saline or Ang II (1000 ng/kg/min for 28 days). DHT administration did not alter serum cholesterol concentrations, lipoprotein distributions, or atherosclerotic lesion areas in either male or female mice. However, administration of DHT increased AAA incidence in male (27% placebo versus 75% DHT) and female mice (28% placebo versus 64% DHT).
  
  
  CONCLUSIONS
  Androgen promotes AT1aR mRNA abundance in abdominal aortas associated with increased Ang II-induced AAAs.
authors.affiliation: Graduate Center for Nutritional Sciences, Room 521b, Wethington Building, 900 S Limestone, University of Kentucky, Lexington, KY 40536-0200, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Henriques
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Frederique B
authors.initials: FB
authors.lastname: Yiannikouris
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
mesh_terms: D000728:Androgens / Q000008:administration & dosage / Q000378:metabolism*; D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000378:metabolism*; D004195:Disease Models, Animal; D004343:Drug Implants; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009919:Orchiectomy; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000728:Androgens; D001057:Apolipoproteins E; D004343:Drug Implants; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D013196:Dihydrotestosterone; D000804:Angiotensin II