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[Genistein represses the induction of prostatic buds by testosterone]
1Département de Sciences fondamentales pour Pharmacie, Faculté des Sciences pharmaceutiques, Teikyo Université, Kanagawa-ken, Japan.
Abstract:
Genistein, a phytoestrogen and a kind of endocrine disrupters, inhibits tyrosine-specific protein kinase activity of the epidermal growth factor (EGF) receptor. It is also effective both in the suppression of the prostatic cell proliferation and the prostate carcinogenesis. We have recently demonstrated that several growth factors, like EGF, transforming growth factor-alpha (TGF-alpha), or keratinocyte growth factor (KGF), can induce prostatic bud formation in the absence of androgen. The present study was performed to investigate whether genistein can suppress testosterone-induced prostatic bud formation. Urogenital sinuses of 16.5-day male rat fetuses were cultured organotypically for 5 days in a serum-free medium containing 10 or 100 ng/ml genistein and 50 ng/ml testosterone. The number and total volume of prostatic buds were analyzed by laser scanning microscopy and computerized. We found that genistein inhibits significantly testosterone-induced prostatic bud formation. In the presence of genistein, cell proliferation of the sinus epithelium was suppressed and the number of prostatic buds and total volume of the buds were reduced as compared with those in the sinuses cultured with testosterone alone. Genistein did not appear to cause necrosis of the sinus. These results support our hypothesis that growth factors like EGF secreted from the sinus mesenchyme activated by testosterone are involved in the induction and stimulation of growth of the prostatic buds.
Insights
Genistein, a phytoestrogen, effectively suppresses testosterone-induced prostate bud formation by inhibiting cell proliferation. This finding supports genistein
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Genistein, a phytoestrogen, inhibits epidermal growth factor (EGF) receptor tyrosine kinase activity.
- Genistein shows potential in suppressing prostate cell proliferation and carcinogenesis.
- Growth factors like EGF, TGF-α, and KGF can induce prostatic bud formation independently of androgens.
Purpose of the Study:
- To investigate the effect of genistein on testosterone-induced prostatic bud formation in developing rat prostates.
Main Methods:
- Organotypic culture of embryonic rat urogenital sinuses (16.5 days gestation).
- Treatment with varying concentrations of genistein (10 or 100 ng/ml) and testosterone (50 ng/ml) in serum-free medium for 5 days.
- Analysis of prostatic bud formation using laser scanning microscopy and computerized measurements of bud number and volume.
Main Results:
- Genistein significantly inhibited testosterone-induced prostatic bud formation.
- Genistein suppressed sinus epithelium cell proliferation, reducing the number and total volume of prostatic buds compared to testosterone alone.
- Genistein did not induce necrosis in the cultured tissue.
Conclusions:
- Genistein suppresses testosterone-induced prostatic bud formation.
- The results suggest that growth factors, such as EGF, activated by testosterone in the sinus mesenchyme, play a role in prostatic bud development.
- Genistein's inhibitory effect on prostatic bud formation warrants further investigation for prostate cancer prevention strategies.