Splanchnic extraction and conversion of testosterone and dihydrotestosterone in man

Area of Science:

• Endocrinology
• Metabolic Studies
• Steroid Hormone Metabolism

Background:

• Testosterone (T) and dihydrotestosterone (DHT) are key androgens with distinct physiological roles.
• Understanding the tissue-specific metabolism and interconversion of these hormones is crucial for comprehending androgen action.
• Previous studies have suggested varying contributions of different organs to T and DHT metabolism.

Purpose of the Study:

• To investigate the splanchnic extraction and interconversion of testosterone and dihydrotestosterone in healthy adult males.
• To quantify the metabolic clearance rates and splanchnic/extrasplanchnic clearances of T and DHT.
• To determine the contribution of the liver to the conversion of testosterone to dihydrotestosterone.

Main Methods:

• Seven healthy men underwent cardiac catheterization for blood sampling.
• Constant infusions of radiolabeled [1,2-3H]testosterone and [4-14C]DHT were administered.
• Arterial and hepatic vein blood samples were analyzed for radioactive and non-radioactive T and DHT to calculate metabolic parameters.

Main Results:

• Splanchnic extraction of testosterone (68.8%) was significantly higher than that of DHT (37.6%).
• Testosterone showed higher splanchnic clearance (638 L/day) compared to DHT (343 L/day), while DHT had higher extrasplanchnic clearance (421 L/day).
• No net appearance of DHT in hepatic vein blood indicated undetectable liver conversion of testosterone to DHT.

Conclusions:

• Testosterone is predominantly metabolized in splanchnic organs, whereas dihydrotestosterone undergoes more extensive extrasplanchnic metabolism.
• The conversion of testosterone to dihydrotestosterone occurs primarily in extrasplanchnic tissues in humans.
• The liver does not significantly contribute to the circulating levels of dihydrotestosterone through testosterone conversion.