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Testosterone modulates renal ammonia metabolism.

Autumn N Harris1,2, Hyun-Wook Lee2, Jill W Verlander2

  • 1Deparment of Small Animal Clinical Science, University of Florida College of Veterinary Medicine, Gainesville, Florida.

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Testosterone significantly impacts kidney size and ammonia metabolism in male mice. Removing testosterone increased ammonia excretion and altered key protein expression, effects reversed by testosterone replacement.

Keywords:
acid-baseammoniaandrogen receptorsex differencestestosterone

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Area of Science:

  • Nephrology
  • Endocrinology
  • Metabolism

Background:

  • Sex differences exist in renal structure and ammonia metabolism.
  • Testosterone, a key male sex hormone, is suspected to influence these differences.

Purpose of the Study:

  • To investigate the role of testis-derived testosterone in sex differences in renal ammonia metabolism and kidney structure.
  • To determine the effects of testosterone on specific proteins involved in renal ammonia generation and transport.

Main Methods:

  • Bilateral orchiectomy (ORCH) was performed on male mice, followed by testosterone replacement therapy.
  • Kidney and proximal tubule size were measured.
  • Ammonia excretion was quantified.
  • Expression levels of key proteins (phosphoenolpyruvate, Na+/K+-2Cl- cotransporter, Na+/H+ exchanger isoform 3) were analyzed.
  • Androgen receptor (AR) cellular expression was examined.

Main Results:

  • Orchiectomy reduced kidney and proximal tubule size, an effect reversed by testosterone replacement.
  • Testosterone deficiency increased ammonia excretion, altered expression of ammonia-generating and reabsorbing proteins, and decreased proximal tubule ammonia secretion.
  • Androgen receptors are present throughout the proximal tubule in both male and female kidneys.

Conclusions:

  • Testosterone plays a critical role in regulating kidney size and ammonia metabolism in male mice.
  • Testosterone influences ammonia generation, reabsorption, and secretion through effects on specific protein expression.
  • The findings suggest testosterone, potentially via ARs, modulates renal function and ammonia handling.