Androgens stimulate proximal tubule transport

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish (US)
JournalGender Medicine
Volume5
Issue numberSUPPL. 1
DOIs
StatePublished - 2008

Fingerprint

Androgens
Angiotensinogen
Angiotensin II
hypertension
Enalaprilat
Hypertension
Injections
Losartan
Inulin
Dihydrotestosterone
Cytochromes
Microvilli
Serum
experiment
Sprague Dawley Rats
Protein Isoforms
Membrane Proteins
Up-Regulation
Perfusion
Western Blotting

Keywords

  • dihydrotestosterone
  • in vivo microperfusion
  • microperfusion
  • proximal tubule
  • renin-angiotensin
  • testosterone

ASJC Scopus subject areas

  • Medicine(all)
  • Gender Studies

Cite this

Androgens stimulate proximal tubule transport. / Quigley, Raymond.

In: Gender Medicine, Vol. 5, No. SUPPL. 1, 2008.

Research output: Contribution to journalArticle

@article{bb58ccb4983643cfa660ec32fc540c77,
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. Conclusion: 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.",
keywords = "dihydrotestosterone, in vivo microperfusion, microperfusion, proximal tubule, renin-angiotensin, testosterone",
author = "Raymond Quigley",
year = "2008",
doi = "10.1016/j.genm.2008.03.011",
language = "English (US)",
volume = "5",
journal = "Gender Medicine",
issn = "1550-8579",
publisher = "Excerpta Medica",
number = "SUPPL. 1",

}

TY - JOUR

T1 - Androgens stimulate proximal tubule transport

AU - Quigley, Raymond

PY - 2008

Y1 - 2008

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

KW - dihydrotestosterone

KW - in vivo microperfusion

KW - microperfusion

KW - proximal tubule

KW - renin-angiotensin

KW - testosterone

UR - http://www.scopus.com/inward/record.url?scp=41449118139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41449118139&partnerID=8YFLogxK

U2 - 10.1016/j.genm.2008.03.011

DO - 10.1016/j.genm.2008.03.011

M3 - Article

C2 - 18395677

AN - SCOPUS:41449118139

VL - 5

JO - Gender Medicine

JF - Gender Medicine

SN - 1550-8579

IS - SUPPL. 1

ER -