|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1996 : ¥1,500,000 (Direct Cost : ¥1,500,000)
On the basis of the working hypothesis that the essential pathogenesis of human benign prostatic hyperplasia might be the stromal proliferation, we are going to investigate how sex hormones and growth factors are involved in the stromal proliferation. We have already established the experimental model for stromal proliferation of male reproductive organs, that is, the stromal proliferation in the seminal vesicle after E2 injection to the immature castrated rats. We investigated the participation of estrogen in the stromal proliferation using this rat seminal vesicle model. On the other hand, in order to obtain the further understanding of the mechanism of stromal proliferation in human benign prostatic hyperplasia, we did the in vitro experiment using the cultured prostate stromal cells. We obtained the following results in 1996.
1) The experimental model : In 1995, we observed that the increase of ER (estrogen receptor) protein in the stromal cells concurred with the stromal proliferat
ion. In 1996, we found that ER protein appeared in the basal cell as well as the stromal cell. Moreover, we found that the concomitant treatment of E2 with 5 alpha-DHT completely inhibited E2 mediated ER expression in both basal cell and stromal cell. This result suggests that ER works only when E2 is given in the absence of 5alpha-DHT.
2) The cultured prostate stromal cell : In 1995, Wwe observed that TGF-beta secretion from the cultured stromal cell increased in proportion to the decrease of DHT concentration in the culture-medium. In 1996, TGF-beta upregulated collagen production from the cultured stromal cell in the autocline fashion. Moreover, we found that this stromal cell had AR (androgen receptor) and expressed KGF in the presence of 5alpha-DHT.This result suggests that there exists DHT-AR-KGF system in this stromal cell.
2) 培養間質細胞での検討:7年度までにヒト前立腺肥大症間質培養細胞で培養液中DHT(dihydrotestosterone)濃度が生理的濃度以下になると、培養細胞からのTGF-β産生が直線的、比例的に増加することを明らかにした。8年度には培養細胞から産生されたTGF-βが培養細胞自身から産生されるコラーゲンを正の調節機構でオートクリン調節していることを再度確認した。この間質培養細胞はARを保有しており、DHT添加によりKGFを発現した。即ちこの間質細胞にDHT-AR-KGF系が存在することを明らかにした(Y.Fukabori et al.,1996)。 Less