scholarly journals Oestrogen and benign prostatic hyperplasia: effects on stromal cell proliferation and local formation from androgen

2008 ◽  
Vol 197 (3) ◽  
pp. 483-491 ◽  
Author(s):  
Clement K M Ho ◽  
Jyoti Nanda ◽  
Karen E Chapman ◽  
Fouad K Habib
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Prostatic Hyperplasia ◽  
Aromatase Activity ◽  
Local Formation ◽  
Cells In Culture ◽  
Prostate Cells ◽  
Prostate Growth

Oestrogens have been implicated as a cause of benign prostatic hyperplasia (BPH). Previous animal studies led to the hypothesis that oestrogens can stimulate prostate growth, resulting in hyperplasia of the gland. In humans, the precise role of oestrogens in BPH pathogenesis is currently unclear. We investigated the direct effects of oestradiol on the proliferation of BPH-derived prostate cells in culture. Oestradiol (10−7 and 10−6 M) moderately increased the proliferation of stromal cells in culture; this stimulation was antagonised by anti-oestrogen ICI 182 780, indicating an oestrogen receptor (ER)-mediated mechanism. By contrast, oestradiol had no effects on the proliferation of epithelial cells in culture. Parameters that can determine the response of stromal cells to oestrogens, including expression of the two ER subtypes and aromatase activity, were investigated. ERβ expression in stromal cells in culture was demonstrated by immunohistochemistry and western blot analysis, and was confirmed by semi-quantitative RT-PCR showing higher expression of ERβ than ERα mRNA in stromal cells. Aromatase, the enzyme that converts androgen precursors to oestrogens, was also examined. Aromatase mRNA and activity were detected in stromal, but not epithelial cells in culture, suggesting a mechanism whereby oestrogen concentrations can be regulated in the BPH stroma. Taken together, these findings support the hypothesis that oestrogens play a role in the pathogenesis of BPH, a disease characterised predominantly by stromal overgrowth.

scholarly journals Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia

2017 ◽  
Vol 5 (5) ◽  
pp. 608-612
Author(s):  
Vanja Filipovski ◽  
Katerina Kubelka-Sabit ◽  
Dzengis Jasar ◽  
Vesna Janevska
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Prostatic Carcinoma ◽  
Growth Control ◽  
Prostatic Hyperplasia ◽  
Receptor Expression ◽  
Stromal Microenvironment ◽  
Histological Score

BACKGROUND: Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa.AIM: To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade.MATERIAL AND METHODS: Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score).RESULTS: AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade.CONCLUSION: AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

scholarly journals Prostatic osteopontin expression is associated with symptomatic benign prostatic hyperplasia

2019 ◽  
Author(s):  
Petra Popovics ◽  
Wisam N. Awadallah ◽  
Sarah Kohrt ◽  
Thomas C. Case ◽  
Nicole L. Miller ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Multispectral Imaging ◽  
Imaging System ◽  
Staining Intensity ◽  
Prostatic Hyperplasia ◽  
Low Grade ◽  
Symptomatic Benign Prostatic Hyperplasia ◽  
Tgf Β1

AbstractBackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often use LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a pro-inflammatory and pro-fibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to pro-inflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone (TZ) of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS i.e. surgical BPH (S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging system and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by ELISA. qPCR was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining (p=0.0107) and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2 and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by pro-inflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of pro-inflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Prostatic stromal cells derived from benign prostatic hyperplasia specimens possess stem cell like property

The Prostate ◽  
2007 ◽  
Vol 67 (12) ◽  
pp. 1265-1276 ◽  
Author(s):  
Victor K. Lin ◽  
Shih-Ya Wang ◽  
Dolores V. Vazquez ◽  
Chet C. Xu ◽  
Sheng Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Prostatic Hyperplasia

scholarly journals Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

2012 ◽  
Vol 214 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Linda Vignozzi ◽  
Ilaria Cellai ◽  
Raffaella Santi ◽  
Letizia Lombardelli ◽  
Annamaria Morelli ◽  
...  
Keyword(s):  
T Cells ◽  
Growth Factors ◽  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Receptor Activation ◽  
Prostatic Hyperplasia ◽  
Serum Testosterone Level ◽  
Antiinflammatory Effect ◽  
Inflammatory Growth

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4+T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4+T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

scholarly journals Vanillic acid attenuates testosterone-induced benign prostatic hyperplasia in rats and inhibits proliferation of prostatic epithelial cells

Oncotarget ◽  
2017 ◽  
Vol 8 (50) ◽  
pp. 87194-87208 ◽  
Author(s):  
Yunu Jung ◽  
Jinbong Park ◽  
Hye-Lin Kim ◽  
Dong-Hyun Youn ◽  
JongWook Kang ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Epithelial Cells ◽  
Vanillic Acid ◽  
Prostatic Hyperplasia

Bladder outlet obstruction

2013 ◽  
pp. 71-126
Author(s):  
John Reynard ◽  
Simon Brewster ◽  
Suzanne Biers
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Diagnostic Tests ◽  
Growth And Development ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Prostatic Hyperplasia ◽  
Benign Prostatic Obstruction ◽  
Prostate Growth ◽  
Symptoms And Signs

Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) 72 Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH 73 Benign prostatic obstruction (BPO): symptoms and signs 74 Diagnostic tests in men with LUTS thought to be due to BPH 76 The management of LUTS in men: NICE 2010 Guidelines ...

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