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Role of dihydrotestosterone in androgen action
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
The Prostate. Supplement
|January 1, 1996
Summary
Dihydrotestosterone (DHT), not testosterone, is the main androgen in target cells, mediating most androgen actions. DHT
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Testosterone is the primary circulating androgen in men.
- Most androgen actions are mediated by dihydrotestosterone (DHT), a metabolite formed within target tissues.
- The enzyme 5alpha-reductase converts testosterone to DHT.
Purpose of the Study:
- To explore the role of dihydrotestosterone (DHT) in mediating androgen action.
- To investigate the significance of DHT's higher binding affinity to the androgen receptor.
- To examine potential roles of circulating DHT as a hormone.
Main Methods:
- Analysis of androgen metabolism pathways.
- Review of evidence on androgen receptor binding affinities.
- Examination of genetic mutations affecting 5alpha-reductase activity and their clinical outcomes.
Main Results:
- DHT, rather than testosterone, is the principal androgen within target cells.
- 5alpha-reductase isoenzymes are crucial for converting testosterone to DHT.
- Mutations in the steroid 5alpha-reductase 2 gene lead to male pseudohermaphroditism; enzyme inhibition causes prostate regression.
Conclusions:
- DHT plays a critical role in androgen action, likely due to its potent binding to the androgen receptor.
- The precise mechanisms and extent to which circulating DHT acts as a hormone remain to be fully elucidated.
- Understanding androgen metabolism is key to explaining various physiological and pathological processes.