Androgens augment proximal tubule transport

Area of Science:

• Nephrology
• Endocrinology
• Physiology

Background:

• The proximal tubule possesses an intrinsic renin-angiotensin system (RAS) regulating transport independently of systemic angiotensin II.
• Androgens are known to elevate angiotensinogen expression, but their impact on proximal tubule transport remains unclear.

Purpose of the Study:

• To investigate the effects of androgens on proximal tubule transport in vivo.
• To determine if androgens influence the intrarenal RAS and its regulation of tubular function.

Main Methods:

• In vivo microperfusion in Sprague-Dawley rats treated with dihydrotestosterone (DHT) or vehicle.
• Assessment of volume reabsorptive rate, effects of angiotensin-converting enzyme and angiotensin receptor inhibitors, renal angiotensinogen and receptor expression, and Na/H exchanger abundance.

Main Results:

• DHT treatment significantly increased proximal tubule volume reabsorptive rate compared to controls.
• Inhibitors of angiotensin II production or action more significantly reduced reabsorption in DHT-treated rats.
• Renal angiotensinogen expression and brush-border Na/H exchanger abundance were elevated in DHT-treated rats, while angiotensin receptor expression and glomerular filtration rate remained unchanged. Blood pressure was higher in DHT-treated rats, with lower serum angiotensin II levels.

Conclusions:

• Androgens may directly upregulate the proximal tubule's renin-angiotensin system.
• Increased proximal tubule reabsorption by androgens contributes to elevated extracellular volume and blood pressure.
• The observed decrease in serum angiotensin II in DHT-treated rats suggests a feedback mechanism.