title: Dehydroepiandrosterone-mediated stimulation of sigma-1 receptor activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding.
abstract: OBJECTIVE
  Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. Using ovariectomized rats, we first defined whether expression of sigma-1 receptor (Sig-1R) in the aorta is regulated following pressure overload (PO) and also after DHEA treatment. We also investigated effects of DHEA known as Sig-1R agonist on impaired Akt/endothelial nitric oxide synthase (eNOS) signaling in the thoracic aorta under PO.
  
  
  METHODS
  Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis 2 weeks later. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after the aortic banding.
  
  
  RESULTS
  Time course study indicated that expression of Sig-1R expression and eNOS decreased time dependently in the thoracic aorta from 1 to 4 weeks after PO. DHEA treatment significantly inhibited the decreased Sig-1R expression in the thoracic aorta. The DHEA treatment also significantly restored PO-induced impaired Akt phosphorylation and stimulated eNOS protein expression with concomitant increased Akt-mediated eNOS phosphorylation (Ser1177). We did not find any changes in the phosphorylation of ERK1/2 and PKCα in the aorta following PO and after treatment with DHEA.
  
  
  CONCLUSIONS
  We here reported, for the first time, that DHEA treatment induces the upregulation and stimulation of Sig-1R in the thoracic aorta that stimulate Sig-1R-mediated Akt-eNOS signaling pathways in ovariectomized rats under PO.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Md Shenuarin
authors.initials: MS
authors.lastname: Bhuiyan
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tagashira
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D010052:Ovariectomy; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000097605:Sigma-1 Receptor
chemical_list: D003687:Dehydroepiandrosterone; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor