Bioavailability of albumin-bound testosterone.

Area of Science:

• Endocrinology
• Pharmacology
• Biochemistry

Background:

• The bioavailability of albumin-bound testosterone is debated.
• Unbound testosterone freely enters tissues, but the role of albumin-bound testosterone is less clear.
• Spironolactone's effect on testosterone binding provided a clinical observation to investigate this.

Purpose of the Study:

• To investigate the effect of albumin binding on testosterone bioavailability.
• To determine if albumin-bound testosterone is biologically active and contributes to tissue uptake.
• To establish a method for measuring bioavailable testosterone.

Main Methods:

• Clinical observation in hirsute women treated with spironolactone.
• Computer modeling to predict changes in testosterone fractions.
• In vitro bioassay using the Oldendorf technique with spironolactone and its metabolites.
• Ammonium sulfate precipitation technique to index non-SHBG-bound testosterone.

Main Results:

• Spironolactone increased the non-SHBG-bound testosterone fraction in plasma.
• Computer modeling indicated a significantly larger increase in albumin-bound testosterone compared to unbound testosterone.
• Bioavailable testosterone increased proportionally with free and albumin-bound testosterone.
• A substantial portion (55%) of albumin-bound testosterone entered tissues, exceeding unbound testosterone's contribution.
• In vitro non-SHBG-bound testosterone correlated strongly with in vitro testosterone bioavailability.

Conclusions:

• Albumin-bound testosterone is biologically important and contributes significantly to testosterone bioavailability.
• The Oldendorf technique and ammonium sulfate precipitation are valid methods for assessing testosterone bioavailability.
• These findings challenge the traditional view that only unbound testosterone is bioavailable.