title: Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution.
abstract: OBJECTIVE
  Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose tissue in humans possibly through binding to oestrogen-receptor-alpha, which in turn activates anti-lipolytic alpha2A-adrenergic-receptor.
  
  
  METHODS
  To address these issues circulating pituitary-gonadal-axis hormones and gene expression of receptors in subcutaneous adipose tissue were determined in 31 nondiabetic HIV-infected male patients receiving HAART (16 with lipodystrophy), in whom measures of fat distribution (CT and DEXA-scans) and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were available.
  
  
  RESULTS
  Total and free oestradiol and testosterone were decreased in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha.
  
  
  CONCLUSIONS
  The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol on the subcutaneous fat depot and lipolysis may be mediated in part through binding to the oestrogen-receptor-alpha, in turn activating anti-lipolytic alpha2A-adrenergic-receptor.
authors.affiliation: Department of Infectious Diseases, Hvidovre University Hospital, DK 2650 Hvidovre, Denmark. oandersen@dadlnet.dk
authors.forename: Ove
authors.initials: O
authors.lastname: Andersen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Birgit
authors.initials: B
authors.lastname: Svenstrup
authors.forename: Birgitte R
authors.initials: BR
authors.lastname: Hansen
authors.forename: Søren K
authors.initials: SK
authors.lastname: Paulsen
authors.forename: Gulla S
authors.initials: GS
authors.lastname: Rathje
authors.forename: Bjørn
authors.initials: B
authors.lastname: Richelsen
authors.forename: Jens Ole
authors.initials: JO
authors.lastname: Nielsen
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Johan
authors.initials: J
authors.lastname: Iversen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001141:Aromatase / Q000235:genetics; D001823:Body Composition; D003430:Cross-Sectional Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D015870:Gene Expression; D005990:Glycerol / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000235:genetics; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007004:Hypoglycemic Agents; D007328:Insulin; D016014:Linear Models; D008066:Lipolysis; D008297:Male; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D050151:Subcutaneous Fat / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D018341:Receptors, Adrenergic, alpha-2; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D001141:Aromatase; D005990:Glycerol; D006854:Hydrocortisone