title: Flutamide increases aldosterone levels in gonadectomized male but not female Wistar rats.
abstract: BACKGROUND
  Sex-specific differences in blood pressure (BP) suggest an important modulating role of testosterone in the kidney. However, little is known about the interaction between androgens and the mineralocorticoid aldosterone. Our objective was to determine the effects of testosterone in gonadectomized male and female rats on a low-salt diet, and to determine the effect of androgen receptor (AR) blockade by flutamide on BP and on aldosterone levels.
  
  
  METHODS
  Normotensive male and female Wistar rats were gonadectomized and put on a low-salt diet. They were treated for 16 days with testosterone or placebo. In addition, the animals received the AR antagonist flutamide or placebo, respectively. BP was measured by tail-cuff method, 24-h urine samples were collected in metabolic cages and blood was collected for hormonal measurements.
  
  
  RESULTS
  Testosterone increased BP in males and females, and this effect could be blocked by flutamide. Flutamide treatment itself significantly increased aldosterone levels in male but not in female rats. These elevated aldosterone levels could be lowered by testosterone treatment during AR blockade. Accordingly to aldosterone levels, flutamide increased in males the serum sodium/potassium to urinary sodium/potassium ratio, an in vivo indicator of renal aldosterone action.
  
  
  CONCLUSIONS
  Testosterone regulates BP in male and female gonadectomized rats via the AR. Flutamide by itself exerts influence over aldosterone in the absence of gonadal steroid replacement suggesting AR involvement in renal sodium handling. These flutamide effects were sex-specific and not seen in female rats.
authors.affiliation: Clinical Endocrinology, Charité Campus Mitte, Berlin, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hofmann
authors.forename: Marten
authors.initials: M
authors.lastname: Michaelis
authors.forename: Franziska
authors.initials: F
authors.lastname: Götz
authors.forename: Christopher
authors.initials: C
authors.lastname: Bartel
authors.forename: Tina
authors.initials: T
authors.lastname: Kienitz
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
mesh_terms: D000450:Aldosterone / Q000097:blood* / Q000652:urine*; D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004039:Diet, Sodium-Restricted; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009919:Orchiectomy; D010052:Ovariectomy; D011188:Potassium / Q000097:blood / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics; D012964:Sodium / Q000097:blood / Q000652:urine; D013739:Testosterone / Q000494:pharmacology
chemical_list: D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; D013739:Testosterone; D000450:Aldosterone; D005485:Flutamide; D012964:Sodium; D011188:Potassium