Relationship between upregulated oestrogen receptors and expression of growth factors in cultured, human, prostatic stromal cells exposed to estradiol or dihydrotestosterone

Abstract

This study investigated the hypothesis that, in benign prostatic hyperplasia (BPH), upregulated oestrogen receptors (ER) and the action of androgens differentially regulate expression of stromal growth factors. Eight human prostatic stromal cell strains were subjected to a procedure to upregulate their ER by exposing them to 1 lmol 17b-estradiol for 10 days followed by passage and growth in the absence of steroids. Four of the cell strains instead received 100 nmol dihydrotestosterone for 48 h. Immunoexpression of ERa, AR and six growth factors was quantified by flow cytometry in each case. Expression of ERa was significantly increased in six of eight cell strains. Expressions of six growth factors (FGF-2, FGF-7, IGF-1, TGF-b 1 NGF and e NOS) were elevated but only for FGF-7 was it significant. There was a significant positive correlation between the change in ERa and the change in FGF-2 and FGF-7, but not the other growth factors. Exposure to dihydrotestosterone reduced expression of ERa and all six growth factors, compared with oestrogentreated cells but not significantly. It is concluded that upregulated ERa in prostatic stroma may have a greater modulating influence on synthesis of certain growth factors than the direct action of androgens and, by enhancing synthesis of FGF-2 and FGF-7, could play a significant role in the development of BPH.

Estrogen induced functional hypertrophy and increased force generation of the female rabbit bladder

“…However, Carley et al [2003] reported that the ERa mRNA expression was signi¢cantly decreased in the mouse bladder after Ovx, which was found to be increased after estrogen replacement and there was no signi¢cant change in the ERb mRNA expression. There are studies showing the upregulation of ERs and expression of growth regulators in cultured prostatic cells exposed to estradiol [Smith et al, 2004]. Our study showed that nerve density decreases after 7 days of estradiol augmentation.…”

Both nongenomic and genomic effects are involved in estradiol's enhancing the phenotype of smooth muscle cells in cultured prostate stromal cells

“…The ratio of estrogen to androgen increases both in the serum and in the prostate gland along with aging of men [4,5], which has a strong correlation with the process of prostate hyperplasia. Many research data have demonstrated that estrogens can regulate the proliferation and differentiation of prostate stromal and epithelial cells [6][7][8][9][10][11][12][13][14][15].…”

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo

“…These specimens were snap-frozen in liquid nitrogen in the operating room and stored at À801C until used for RNA extraction. Patients with BPH or low-grade prostatic intraepithelial neoplasia (PIN) with no evident CaP (following thorough histopathological examination 25 ) were defined as 'non-CaP'. 'PIN' was defined morphologically, and distinguished from carcinoma, according to established criteria.…”