scholarly journals Transcript Profiling of the Androgen Signal in Normal Prostate, Benign Prostatic Hyperplasia, and Prostate Cancer

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5806-5816 ◽  
Author(s):  
David R. Bauman ◽  
Stephan Steckelbroeck ◽  
Donna M. Peehl ◽  
Trevor M. Penning
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Cell Types ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Rt Pcr ◽  
Retinol Dehydrogenase ◽  
Normal Prostate ◽  
Androgen Ablation

Human prostate adenocarcinoma (CaP) and benign prostatic hyperplasia (BPH) have epithelial and stromal cell origins, respectively. To determine whether the androgen signal is processed differently in these cell types the expression of transcripts for enzymes that control ligand access to the androgen receptor (AR) were measured. Transcripts for type 2 5α-reductase, ketosteroid reductases [aldo-keto reductase (AKR)1C1-AKR1C4], the major oxidative 3α-hydroxysteroid dehydrogenase (HSD) retinol dehydrogenase (RODH)-like 3α-HSD (RL-HSD) and nuclear receptors [AR, estrogen receptor (ER)α, and ERβ] were determined in whole human prostate and in cultures of primary epithelial cells (PEC) and primary stromal cells (PSC) from normal prostate, CaP and BPH by real-time RT-PCR. Normal PEC (n = 14) had higher levels of AKR1C1 (10-fold, P < 0.001), AKR1C2 (115-fold, P < 0.001) and AKR1C3 (6-fold, P < 0.001) than normal PSC (n = 15), suggesting that reductive androgen metabolism occurs. By contrast, normal PSC had higher levels of AR (8-fold, P < 0.001) and RL-HSD (21-fold, P < 0.001) than normal PEC, suggesting that 3α-androstanediol is converted to 5α-dihydrotestosterone to activate AR. In CaP PEC (n = 14), no significant changes in transcript levels vs. normal PEC were observed. In BPH PSC (n = 21) transcripts for AR (2-fold, P < 0.001), AKR1C1 (4-fold, P < 0.001), AKR1C2 (10-fold P < 0.001), AKR1C3 (4-fold, P < 0.001) and RL-HSD (3-fold, P < 0.003) were elevated to increase androgen response. Differences in the AR:ERβ transcript ratios (eight in normal PEC vs. 280 in normal PSC) were maintained in PEC and PSC in diseased prostate. These data suggest that CaP may be more responsive to an ERβ agonist and BPH may be more responsive to androgen ablation.

scholarly journals Estrogen receptors alpha and beta in the normal, hyperplastic and carcinomatous human prostate

2001 ◽  
Vol 168 (3) ◽  
pp. 447-454 ◽  
Author(s):  
M Royuela ◽  
MP de Miguel ◽  
FR Bethencourt ◽  
M Sanchez-Chapado ◽  
B Fraile ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Stromal Cells ◽  
Normal Function ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Estrogen Action ◽  
Normal Prostate ◽  
New Information ◽  
Long Time ◽  
Er Alpha

Two different estrogen receptors (ER-alpha and ER-beta) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ER-alpha was considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-alpha in the three types of prostatic specimens studied. Epithelial immunostaining for ER-beta was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-beta was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.

scholarly journals Extracts of Phyllostachys pubescens Leaves Represses Human Steroid 5-Alpha Reductase Type 2 Promoter Activity in BHP-1 Cells and Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia in Rat Model

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 884
Author(s):  
Kwang Hoon Song ◽  
Chang-Seob Seo ◽  
Won-Kyung Yang ◽  
Hyun-O Gu ◽  
Ki-Joong Kim ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Mrna Expression ◽  
Rat Model ◽  
Promoter Activity ◽  
Prostatic Hyperplasia ◽  
Human Prostate ◽  
Phyllostachys Pubescens ◽  
Prostate Cell ◽  
Srd5a2 Gene

Benign prostatic hyperplasia (BPH) is the most common symptomatic abnormality of the human prostate characterized by uncontrolled proliferation of the prostate gland. In this study, we investigated the effect of bamboo, Phyllostachys pubescens, leaves extract (PPE) on human 5α-reductase type 2 (SRD5A2) gene promoter activity in human prostate cell lines and the protective effect of PPE on a testosterone-induced BPH rat model. PPE repressed human SRD5A2 promoter activity and its mRNA expression. The rats treated with PPE for 4 weeks showed a significantly attenuated prostate weight compared to vehicle control. PPE-treated rats also showed reduced serum dihydrotestosterone, testosterone, prostate-specific antigen, and SRD5A2 levels by testosterone injection. Quantitative real-time polymerase chain reaction showed that PPE treatment significantly decreased mRNA expression of SRD5A2, androgen receptor (AR), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor 2 compared with the vehicle-treated, testosterone-injected rats in the prostate. Furthermore, PPE treatment showed reduced AR, PCNA, and tumor necrosis factor alpha expression in the prostate via immunohistofluorescence staining. In conclusion, oral administration of PPE prevented and inhibited the development and progression of enlarged prostate lesions in testosterone-induced animal models through various anti-proliferative and anti-inflammatory pharmacological effects and induced suppression of SRD5A2 gene expression.

scholarly journals 17β-Estradiol at Low Concentrations Acts through Distinct Pathways in Normal Versus Benign Prostatic Hyperplasia-Derived Prostate Stromal Cells

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4594-4605 ◽  
Author(s):  
Irwin I. Park ◽  
Qiang Zhang ◽  
Victoria Liu ◽  
James M. Kozlowski ◽  
Ju Zhang ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Stromal Cells ◽  
Cell Types ◽  
Prostatic Hyperplasia ◽  
Low Concentrations ◽  
17Β Estradiol ◽  
Mapk Inhibitors ◽  
Subsequent Activation ◽  
Estrogen Receptor Antagonists ◽  
Rapid Signaling

Abstract The aim of this study was to identify differential responses to low concentrations of 17β-estradiol (E2) in primary stromal cell cultures derived from either normal organ donors or benign prostatic hyperplasia or hypertrophy (BPH) specimens. Furthermore, we sought to identify the potential mechanism of E2 action in these cell types, through either a genomic or nongenomic mechanism. We initially treated stromal cells derived from five normal prostates or five BPH specimens with low concentrations of E2 (0.001–1.0 nm) and analyzed their growth response. To determine whether genomic or nongenomic pathways were involved, we performed studies using specific estrogen receptor antagonists to confirm transcriptional activity or MAPK inhibitors to confirm the involvement of rapid signaling. Results of these studies revealed a fundamental difference in the mechanism of the response to E2. In normal cells, we found that a nongenomic, rapid E2 signaling pathway is predominantly involved, mediated by G protein-coupled receptor-30 and the subsequent activation of ERK1/2. In BPH-derived prostate stromal cells, a genomic pathway is predominantly involved because the addition of ICI 182780 was sufficient to abrogate any estrogenic effects. In conclusion, prostate stromal cells respond to far lower concentrations of E2 than previously recognized or examined, and this response is mediated through two distinct mechanisms, depending on its origin. This may provide the basis for new insights into the causes of, and possible treatments for, BPH.

scholarly journals MP06-01 IDENTIFICATION OF COGNATE PROXIMAL CELL TYPES OF THE MOUSE AND HUMAN PROSTATE AND THEIR ENRICHMENT IN HUMAN BENIGN PROSTATIC HYPERPLASIA

2020 ◽  
Vol 203 ◽  
pp. e51
Author(s):  
Diya Binoy Joseph ◽  
Gervaise Henry ◽  
Alicia Malewska ◽  
Kyle Wegner ◽  
Jeffrey Reese ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Cell Types ◽  
Prostatic Hyperplasia ◽  
Human Prostate
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