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Related Experiment Videos

Quantal relationship between prostatic dihydrotestosterone and prostatic cell content: critical threshold concept.

N Kyprianou1, J T Isaacs

  • 1Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

The Prostate
|January 1, 1987
PubMed
Summary

Prostate cell growth is triggered by dihydrotestosterone (DHT) only after a critical threshold is met, not continuously. Lowering DHT below this threshold is sufficient to halt prostate cell proliferation.

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Area of Science:

  • Endocrinology
  • Urology
  • Cell Biology

Background:

  • Androgens, particularly dihydrotestosterone (DHT), play a crucial role in prostate development and function.
  • Understanding the dose-response relationship of androgens in regulating prostatic cell number is key to managing prostate diseases.

Purpose of the Study:

  • To determine if androgen-induced prostatic cell proliferation is a continuous graded response or a quantal, threshold-dependent process.
  • To establish the critical threshold of prostatic DHT required to initiate cell number increase in rats.

Main Methods:

  • Constructed a prostatic DHT dose versus prostatic cell number response curve in rats.
  • Utilized castrated-adrenalectomized rats, untreated castrated rats, and rats with testosterone implants of varying lengths.

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  • Covered a range of prostatic DHT levels from undetectable to pharmacologically high.

    • Main Results:

    • The dose-response curve was sigmoidal, not continuously hyperbolic, indicating a non-linear relationship.
    • Prostatic cell number increase was observed only when prostatic DHT concentration exceeded a critical threshold.
    • The critical threshold for the rat ventral prostate was determined to be 0.4 ng/10(8) cells.

    Conclusions:

    • Androgen-induced prostatic cell proliferation in rats is a quantal process, requiring DHT to surpass a specific threshold.
    • To inhibit prostate cell growth, prostatic DHT levels must be reduced below this critical threshold.
    • Complete elimination of DHT is not necessary to prevent androgenic stimulation of prostatic cell number.