Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia

Purpose: To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of ratsMethods: BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65.Results: Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone.Conclusions: Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

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Effect of the steroidal androgen receptor antagonist win 49,596 on steroid-induced benign prostatic hyperplasia in the castrate beagle dog

The Prostate ◽

10.1002/pros.2990160102 ◽

1990 ◽

Vol 16 (1) ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

P. E. Juniewicz ◽

B. M. Lemp ◽

T. A. Barbolt ◽

T. K. Labrie ◽

M. McCarthy ◽

...

Keyword(s):

Androgen Receptor ◽

Benign Prostatic Hyperplasia ◽

Receptor Antagonist ◽

Prostatic Hyperplasia ◽

Beagle Dog ◽

Androgen Receptor Antagonist

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The Effect of Zanoterone, a Steroidal Androgen Receptor Antagonist, in Men with Benign Prostatic Hyperplasia

The Journal of Urology ◽

10.1016/s0022-5347(01)66976-3 ◽

1995 ◽

Vol 154 (3) ◽

pp. 1060-1064 ◽

Cited By ~ 8

Author(s):

Bruce M. Berger ◽

Amirtha Naadimuthu ◽

Alexander Boddy ◽

Hugh A. Fisher ◽

John D. McConnell ◽

...

Keyword(s):

Androgen Receptor ◽

Benign Prostatic Hyperplasia ◽

Receptor Antagonist ◽

Prostatic Hyperplasia ◽

Androgen Receptor Antagonist

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The Effect of Zanoterone, a Steroidal Androgen Receptor Antagonist, in Men with Benign Prostatic Hyperplasia

The Journal of Urology ◽

10.1097/00005392-199509000-00043 ◽

1995 ◽

pp. 1060-1064 ◽

Cited By ~ 1

Author(s):

Bruce M. Berger ◽

Amirtha Naadimuthu ◽

Alexander Boddy ◽

Hugh A. Fisher ◽

John D. McConnell ◽

...

Keyword(s):

Androgen Receptor ◽

Benign Prostatic Hyperplasia ◽

Receptor Antagonist ◽

Prostatic Hyperplasia ◽

Androgen Receptor Antagonist

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Angiotensin II enhances noradrenaline release from sympathetic nerves of the rat prostate via a novel angiotensin receptor: implications for the pathophysiology of benign prostatic hyperplasia

Journal of Endocrinology ◽

10.1677/joe.0.1710097 ◽

2001 ◽

Vol 171 (1) ◽

pp. 97-108 ◽

Cited By ~ 29

Author(s):

ME Fabiani ◽

M Sourial ◽

WG Thomas ◽

CI Johnston ◽

...

Keyword(s):

Benign Prostatic Hyperplasia ◽

Receptor Antagonist ◽

Functional Role ◽

Sympathetic Nerves ◽

Prostatic Hyperplasia ◽

Facilitatory Effect ◽

Ang Ii ◽

Sympathetic Transmission ◽

Rat Prostate ◽

Na Release

The renin-angiotensin system (RAS) is present in the human prostate and may be activated in benign prostatic hyperplasia (BPH), possibly contributing to the pathophysiology of this disorder by enhancing local sympathetic tone and cell growth. The functional role of the RAS in the prostate, however, is unknown. The present study was undertaken to determine whether angiotensin (Ang) II enhances sympathetic transmission in the prostate. The neuronal stores of the rat prostate were labelled with [(3)H]noradrenaline (NA). Ang II and Ang I enhanced [(3)H]NA release in a concentration-dependent manner. The Ang II receptor subtype 1 (AT(1) receptor) antagonist losartan and the AT(2) receptor antagonist PD123319 inhibited this facilitatory effect of Ang II and Ang I, whereas the other AT(2) receptor antagonist, CGP42112, was without effect. Bradykinin also increased [(3)H]NA release, which was inhibited by the B(2) receptor antagonist Hoe140. The angiotensin-converting enzyme inhibitor captopril inhibited the effect of Ang I, but potentiated that of bradykinin. Interestingly, captopril alone produced an increase in [(3)H]NA release which was inhibited by Hoe140. Losartan, but not PD123319 or CGP42112, inhibited [(125)I]-Ang II binding in Chinese hamster ovary cells transfected with the AT(1a) or AT(1b) receptor. In contrast, in cells expressing the AT(2) receptor, PD123319 and CGP42112, but not losartan, inhibited [(125)I]-Ang II binding. In conclusion, Ang II enhances the release of NA from sympathetic nerves of the rat prostate via a novel functional receptor distinct from the cloned AT(1a), AT(1b) or AT(2). These data provide direct evidence in support of a functional role for the local RAS in modulating sympathetic transmission in the prostate, which may have important implications for the pathophysiology of BPH.

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Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF-β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6281819 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Wenfan Chen ◽

Xiaoqing Huang ◽

Axiang Peng ◽

Tingting Chen ◽

Renzhi Yang ◽

...

Keyword(s):

Benign Prostatic Hyperplasia ◽

Signaling Pathway ◽

Testosterone Propionate ◽

Prostatic Hyperplasia ◽

Prostate Tissue ◽

Control Group ◽

Smad Signaling ◽

Smad Signaling Pathway ◽

Wet Weight ◽

Kangquan Recipe

Background. Kangquan Recipe (KQR) is a traditional Chinese medicine compound made by our research group for the treatment of benign prostatic hyperplasia (BPH). Whether KQR can treat BPH as a single drug or play a role in the treatment of BPH in combination therapy needs further study. Aim of the Study. To investigate the effect of KQR on the expression of TGF-β/Smad signaling pathway-related factors in rats with BPH. In-depth analysis revealed the relevant signal transduction mechanism by which KQR acts to treat BPH. Materials and Methods. Forty-eight male Sprague-Dawley rats were randomly divided into six groups of 8 rats each. In addition to the control group, 40 rats were castrated and then injected with testosterone propionate to form a prostatic hyperplasia model. After 30 days, three groups received different concentrations of KQR (14 g/kg, 7 g/kg, and 3.5 g/kg), and the finasteride group received 0.5 mg/kg finasteride. The BPH group and the control group received the same volume of saline. All groups were treated for a total of 30 days. Rat body weight, prostate volume, wet weight, index, histology, and the mRNA and protein levels of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, BAMBI, E-cadherin, and N-cadherin in the prostate tissue were measured after the end of treatment. Results. Compared with the control group, the BPH group had increased prostate wet weight, volume, and index, and the histology showed significant BPH. Compared with the BPH group, the three KQR groups and the finasteride group all had varying levels of reduction in the prostate wet weight, volume, and index of the prostate and varying degrees of improvement in the histological manifestations of BPH. KQR downregulates the mRNA and/or protein expression of TGF-β, TGF-βR1, TGF-βR2, p-Smad2, p-Smad3, and N-cadherin protein in prostate tissue and increases the mRNA and protein expression of BAMBI and E-cadherin protein. Conclusions. In the model of BPH induced by testosterone propionate after castration, KQR can inhibit the conduction of the TGF-β/Smad signaling pathway by upregulating the expression of BAMBI protein and reversing EMT in rat prostate tissue.

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