title: Differential regulation of aortic growth in male and female rodents is associated with AAA development.
abstract: BACKGROUND
  The objective was to examine effects of gonadal hormone manipulation on aortic diameter and macrophage infiltration in rodents during abdominal aortic aneurysm (AAA) formation.
  
  
  METHODS
  Experiment 1: 17-beta estradiol and testosterone pellets were implanted in male (ME) and female (FT) rats. No pellet was implanted in shams (MES, FTS). Experiment 2: Testes and ovaries were removed from males (MO) and females (FO), respectively. No organs were removed from shams (MOS, FOS). Experiment 3: Male and female rats were orchiectomized and oophorectomized, respectively. Four weeks post-castration, testosterone (MOT) and 17-beta estradiol (FOE) pellets were implanted. Shams underwent castration, but no pellet was implanted (MOTS, FOES). All rats underwent infrarenal aortic infusion with elastase postimplantation/postcastration. Diameters were measured on postoperative d 14. Tissue was stained for macrophages by immunohistochemistry.
  
  
  RESULTS
  Diameter (P = 0.046) and macrophage counts (P = 0.014) decreased in ME compared with shams, but not in females treated with testosterone (FT). Diameter (P = 0.019) and macrophage infiltration (P = 0.024) decreased in MO compared with shams, but not in FO. Diameter increased in MOT compared with MOTS (P = 0.033), but decreased in FOE compared with FOES (P = 0.002). Macrophages decreased in FOE compared with FOES (P = 0.002).
  
  
  CONCLUSIONS
  This study documents a decrease in AAA diameter in males treated with estrogen or undergoing orchiectomy, but no changes in females treated with testosterone or undergoing oophorectomy; and an increase in diameter in MOT and a decrease in FOE. These data suggest that gonadal hormones differentially regulate AAA growth in association with changes in macrophages.
authors.affiliation: Department of Biomedical Engineering, Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Brenda S
authors.initials: BS
authors.lastname: Cho
authors.forename: Derek T
authors.initials: DT
authors.lastname: Woodrum
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Roelofs
authors.forename: James C
authors.initials: JC
authors.lastname: Stanley
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000009:adverse effects; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D013739:Testosterone; D004958:Estradiol; D010196:Pancreatic Elastase