title: Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.
abstract: OBJECTIVE
  To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men.
  
  
  METHODS
  Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed.
  
  
  RESULTS
  DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production.
  
  
  CONCLUSIONS
  We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.
authors.affiliation: Center for Bone Research at the Sahlgrenska Academy (CBS), Department of Internal Medicine, Göteborg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Movérare-Skrtic
authors.forename: Katrien
authors.initials: K
authors.lastname: Venken
authors.forename: Niklas
authors.initials: N
authors.lastname: Andersson
authors.forename: Marie K
authors.initials: MK
authors.lastname: Lindberg
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Swanson
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Jan
authors.initials: J
authors.lastname: Oscarsson
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002153:Calorimetry, Indirect; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D013196:Dihydrotestosterone / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced*; D009919:Orchiectomy / Q000009:adverse effects*; D011944:Receptors, Androgen / Q000502:physiology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D014280:Triglycerides; D013196:Dihydrotestosterone; D002784:Cholesterol