title: Endogenous androgen deficiency enhances diet-induced hypercholesterolemia and atherosclerosis in low-density lipoprotein receptor-deficient mice.
abstract: BACKGROUND
  Despite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial.
  
  
  OBJECTIVE
  We sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol.
  
  
  METHODS
  Male and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development.
  
  
  RESULTS
  Female mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice.
  
  
  CONCLUSIONS
  These data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice in response to a low-fat diet.
authors.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Hatch
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Srodulski
authors.forename: Huei-Wei
authors.initials: HW
authors.lastname: Chan
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Tannock
authors.forename: Victoria L
authors.initials: VL
authors.lastname: King
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D018752:Diet, Fat-Restricted; D005260:Female; D006937:Hypercholesterolemia / Q000378:metabolism*; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D051379:Mice; D011973:Receptors, LDL / Q000235:genetics; D012737:Sex Factors
chemical_list: D000728:Androgens; D008055:Lipids; D008077:Lipoproteins, LDL; D011973:Receptors, LDL