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A new approach to prostate cancer
Y Z Ito1, Y Nakazato, V Petrow
1College of Medical Care and Technology, Gunma University, Department of Pathology, Gunma University School of Medicine, Japan.
The Journal of Pharmacy and Pharmacology
|July 1, 1989
Summary
6-methyleneprogesterone inhibits human prostate cancer growth by blocking the conversion of testosterone to dihydrotestosterone. This suggests dihydrotestosterone is the key androgen driving prostate tumor progression.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Androgen-dependent human prostatic adenocarcinoma growth is a significant clinical challenge.
- Testosterone and dihydrotestosterone are key androgens regulating prostate function and neoplasia.
- Inhibitors of 5 alpha-reductase are potential therapeutic agents for prostate cancer.
Purpose of the Study:
- To investigate the effect of 6-methyleneprogesterone on androgen-dependent human prostatic adenocarcinoma growth in vivo.
- To determine the mechanism of action of 6-methyleneprogesterone, specifically its effect on 5 alpha-reductase activity and androgen levels.
Main Methods:
- Implantation of human prostatic adenocarcinoma (Honda tumour) in nude mice.
- Administration of 6-methyleneprogesterone.
- In vitro and in vivo assessment of 5 alpha-reductase inhibition.
- Measurement of circulating luteinizing hormone (LH) and testosterone levels.
Main Results:
- 6-methyleneprogesterone significantly inhibited the growth of the Honda tumour.
- The steroid demonstrated potent inhibition of both rat and human prostatic 5 alpha-reductase in vitro.
- In vivo, 6-methyleneprogesterone reduced the metabolic conversion of testosterone to dihydrotestosterone.
- Minimal effects were observed on circulating LH and testosterone levels.
Conclusions:
- Dihydrotestosterone, not testosterone, is the primary trophic androgen for human prostatic neoplasms.
- 6-methyleneprogesterone is a potential therapeutic agent for prostate cancer due to its ability to inhibit dihydrotestosterone synthesis.
- Targeting dihydrotestosterone production offers a promising strategy for managing androgen-dependent prostate cancer.