La génistéine réprime l’induction des bourgeons prostatiques par la testostérone

Genistein inhibits testosterone-induced prostatic bud formation

Département de Sciences fondamentales pour Pharmacie, Faculté des Sciences pharmaceutiques, Teikyo Université, Sagamiko, Tsukui-gun, Kanagawa-ken, 199-0195, Japon

Résumé

Nous avons étudié l’induction des bourgeons prostatiques dans le sinus urogénital d’embryons de Rat cultivé en présence de testostérone et de génistéine, un inhibiteur de l’activité du récepteur du facteur de croissance de l’épiderme (EGF). Il a été observé que la génistéine peut exercer son action inhibitrice sur la prolifération des cellules de l’épithélium du sinus et l’induction des bourgeons prostatiques provoquées par la testostérone. Les résultats confirment notre hypothèse que les facteurs de croissance tels que l’EGF, sécrétés par le mésenchyme du sinus activé par la testostérone, provoquent la formation de bourgeons prostatiques dans le sinus fœtal.

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-α (TGF-α), 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.