Autoradiographic studies of androgen-binding sites in human benign prostatic hyperplasia in vitro

1989 ◽  
Vol 120 (1) ◽  
pp. 167-NP ◽  
Author(s):  
I. Lasnitzki ◽  
H. Takeda ◽  
T. Mizuno
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Binding Sites ◽  
Prostatic Hyperplasia ◽  
Secretory Cells ◽  
Basal Cells ◽  
Luminal Side ◽  
Cell Layers ◽  
Androgen Binding

ABSTRACT Steroid autoradiographic techniques were used to visualize the distribution of androgen receptor-positive cells in human benign prostatic hyperplasia grown in organ culture. The tissue consisted of alveoli embedded in dense fibromuscular stroma and lined either with one row of cuboidal secretory cells or with several layers of epithelial cells. In some explants alveoli were seen lined with spindle-shaped cells. The autoradiographs showed that in most explants both epithelium and stroma contained androgen receptor-positive cells but that the uptake was less pronounced in the stromal cells. In alveoli lined with several cell layers the basal cells seemed to incorporate less androgen than secretory cells on the luminal side. In alveoli lined with spindle-shaped cells, these were always androgen receptor-negative. Journal of Endocrinology (1989) 120, 167–170

Stroma of human benign prostatic hyperplasia: preferential tissue for androgen metabolism and oestrogen binding

1981 ◽  
Vol 96 (3) ◽  
pp. 422-432 ◽  
Author(s):  
M. Krieg ◽  
G. Klötzl ◽  
J. Kaufmann ◽  
K. D. Voigt
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Binding Sites ◽  
Reductase Activity ◽  
Enzyme Reaction ◽  
Prostatic Hyperplasia ◽  
Binding Studies ◽  
Normal Prostate ◽  
Layer Chromatography ◽  
Androgen Binding ◽  
Tissue Fraction

Abstract. Because of the well known stromal-epithelial interaction of various urogenital organs, it was of interest to compare quantitatively steroid metabolism and binding in epithelium (E) and stroma (S) of the human benign prostatic hyperplasia (BPH). Testosterone 5α-reductase activity was determined by thin-layer chromatography and androgen as well as oestrogen binding sites by a charcoal adsorption technique after a steroid incubation period of 18 h at 0°C, using methyltrienolone (R1881) and oestradiol-17β as tritiated ligands and unlabelled R1881 and diethylstilboestrol as the respective competitors. The main results were as follows: (1) using biochemical markers (acid phosphatase, hydroxyproline), an on average 17% contamination of E by S and 6% of S by E was found, (2) the molar optimum of NADPH for the enzyme reaction was nearly identical in E and S, ranging between 1 and 0.1 mm, (3) the apparent Michaelis constant (Km) of 5α-reductase was in both fractions identical, the mean being 0.15 (μm, (4) the maximal rate of 5α-reductase activity (pmol 5α-reduced metabolites · mg protein−1 · 1 h−1) was 161 ± 28 (sem; n = 20), 66 ± 4.6 and 148 ± 6.6 in S, E and whole tissue fraction of BPH, respectively. In two normal prostates the means were: 88, 53 and 73, respectively, (5) the androgen binding sites were evenly distributed between the cytosol of E and S, while measurable oestrogen binding sites were found in 42% of the analyzed S but only in 5% of analyzed E. In conclusion: the 2.4 times higher 5·-reductase activity in S compared to E of the BPH is responsible for the about 2 to 2.5 times higher activity in the whole tissue fraction of BPH if compared with the normal prostate. Furthermore, due to our preliminary binding studies, oestrogens might play an important role in the S fraction of BPH.

The CAG Repeat Within the Androgen Receptor Gene and Benign Prostatic Hyperplasia

1999 ◽  
Vol 162 (1) ◽  
pp. 269-270
Author(s):  
E. Giovannucci ◽  
E.A. Platz ◽  
M.J. Stampfer ◽  
A. Chan ◽  
K. Krithivas ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Receptor Gene ◽  
Androgen Receptor Gene ◽  
Prostatic Hyperplasia ◽  
Cag Repeat

scholarly journals Functional mapping of androgen receptor enhancer activity

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Chia-Chi Flora Huang ◽  
Shreyas Lingadahalli ◽  
Tunc Morova ◽  
Dogancan Ozturan ◽  
Eugene Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Binding Sites ◽  
Gene Promoters ◽  
Strongly Correlated ◽  
Enhancer Activity ◽  
Drive Gene Expression ◽  
In Vitro Cell Lines ◽  
Drive Gene

Abstract Background Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10–100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription. Results To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity. Conclusions Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.

scholarly journals The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review

2020 ◽  
Vol 7 (3) ◽  
pp. 191-202 ◽  
Author(s):  
Renee E. Vickman ◽  
Omar E. Franco ◽  
Daniel C. Moline ◽  
Donald J. Vander Griend ◽  
Praveen Thumbikat ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Hyperplasia ◽  
Prostate Development

scholarly journals Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 450
Author(s):  
Kensuke Mitsunari ◽  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Molecular Mechanisms ◽  
Prostatic Hyperplasia ◽  
Pathological Conditions ◽  
Urinary Tract Symptoms ◽  
Anti Inflammatory ◽  
Lower Urinary

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

scholarly journals The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1

2016 ◽  
Vol 41 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Guan-Yu Ren ◽  
Chun-Yang Chen ◽  
Wei-Guo Chen ◽  
Ya Huang ◽  
Li-Qiang Qin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Estrogen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
G Protein ◽  
Therapeutic Potential ◽  
Prostatic Hyperplasia ◽  
Docking Simulations ◽  
G Protein Coupled

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

Sex difference in the cytosolic and nuclear distribution of androgen receptor in mouse submandibular gland

1986 ◽  
Vol 108 (2) ◽  
pp. 267-273 ◽  
Author(s):  
S. Kyakumoto ◽  
R. Kurokawa ◽  
Y. Ohara-Nemoto ◽  
M. Ota
Keyword(s):  
Androgen Receptor ◽  
Nuclear Receptors ◽  
Binding Sites ◽  
Androgen Receptors ◽  
Dissociation Constants ◽  
Scatchard Analysis ◽  
Male And Female ◽  
Short Period ◽  
Almost All ◽  
Androgen Binding

ABSTRACT Cytosol and nuclear androgen receptors in submandibular glands of male and female mice were measured by an exchange assay at 0 °C. The binding of [3H]methyltrienolone to cytosol receptors in females was mostly saturated within a short period of incubation (3 h), whereas the saturation was much slower in males; suggesting that almost all of the cytosol receptors were unoccupied in females and the receptors were partially occupied in males. Nuclear receptors were extracted with pyridoxal 5′-phosphate (5 mmol/l) from nuclear fractions with 93–95% efficiency. The exchange of the bound steroids occurred by 24–48 h at 0 °C, suggesting that most of the nuclear androgen receptor was occupied. The binding was low at higher temperatures, probably due to inactivation of the receptor. Scatchard analysis showed that the apparent dissociation constants of cytosol and nuclear receptors were similar (0·8 and 0·9 nmol/l respectively) in both sexes. On the other hand, the number of androgen-binding sites in the nucleus was much higher in males than in females (1052 fmol/mg DNA and 32 fmol/mg DNA respectively), while the number in the cytosol was higher in females than in males (512 fmol/mg DNA and 368 fmol/mg DNA respectively). These observations show that androgen receptors exist mainly (74%) in the nuclei of males, while they exist mostly (94%) in the cytosol of females. J. Endocr. (1986) 108, 267–273

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.

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