title: Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers.
abstract: BACKGROUND
  Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERalpha) and androgen receptor (AR) expression.
  
  
  RESULTS
  In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERalpha and AR in nuclear extracts of vaginal tissue from diabetic animals.
  
  
  CONCLUSIONS
  In ovariectomized (estrogen deficient) animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERalpha, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal.
authors.affiliation: Institute for Sexual Medicine, Department of Urology, Boston University School of Medicine, Boston, USA. nnkim@bu.edu
authors.forename: Noel N
authors.initials: NN
authors.lastname: Kim
authors.forename: Miljan
authors.initials: M
authors.lastname: Stankovic
authors.forename: Tulay T
authors.initials: TT
authors.lastname: Cushman
authors.forename: Irwin
authors.initials: I
authors.lastname: Goldstein
authors.forename: Ricardo
authors.initials: R
authors.lastname: Munarriz
authors.forename: Abdulmaged M
authors.initials: AM
authors.lastname: Traish
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012039:Regional Blood Flow; D014621:Vagina / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D052250:Nitric Oxide Synthase Type III; D017869:Cyclic GMP-Dependent Protein Kinases; D001119:Arginase