title: Androgens stimulate proximal tubule transport.
abstract: BACKGROUND
  Disrupting the enzyme cytochrome P4a14 in mice leads to hypertension, which is more severe in male than in female mice and appears to be due to androgen excess. Androgens are known to increase expression of angiotensinogen,but the effect of androgens on proximal tubule transport is unknown.
  
  
  OBJECTIVE
  These studies aimed to determine the effect of androgens on proximal tubule transport.
  
  
  METHODS
  Proximal tubules from knockout (KKO) and wild-ttype (WWT) (SSV/1129) mice were perfused in vitro. Volume resorption (JJ v ) was measured using 3 H-methoxy inulin as a volume marker. In separate experiments, male Sprague-Dawley rats were given dihydrotestosterone (DDHT) injections IP for 10 days. Proximal tubule transport was measured in this model using in vivo microperfusion. The renal expression of angiotensinogen was measured by Northern analysis, and brush border membrane protein abundance of the sodium-hhydrogen exchanger isoform 3 (NNHE3) was measured by Western blotting in the control and DHT-ttreated rats.
  
  
  RESULTS
  Mean (SSE) Jv was significantly elevated in proximal tubules from KO mice compared with WT mice (11.11 [0.006] vs 0.77 [0.112] nL/mm . mm, respectively; P<0.05). The mean proximal tubule Jv rate was significantly higher in DHT-ttreated rats than in control rats given vehicle injections (44.57 [0.331] vs 3.31 [0.223] nL/mm . min, respectively; P<0.01). Luminal perfusion with either enalaprilat or losartan decreased the proximal tubule J v rate in DHT-ttreated rats to a greater degree than in control rats. The DHT-treated rats had higher blood pressures and lower serum angiotensin II concentrations than did the control rats.
  
  
  CONCLUSIONS
  Results suggest that androgens may directly upregulate the proximal tubule reninangiotensin system, increase the expression of NHE3, and increase the Jv rate, thereby increasing extracel-lular volume and blood pressure and secondarily decreasing serum angiotensin II concentrations.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA. Raymond.Quigley@UTSouthwestern.edu
authors.forename: Raymond
authors.initials: R
authors.lastname: Quigley
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006973:Hypertension / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000728:Androgens; C000613386:Slc9a3 protein, mouse; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013196:Dihydrotestosterone; D000804:Angiotensin II