Oral exposure of sulpiride promotes the proliferation of Brown‑Norway rat prostates

Zheng,Chengcheng; Luo,Yongwei; Chen,Ying; Chen,Dingshi; Shao,Congcong; Huang,Dongyan; Zhu,Jing; Mao,Xiaoyan; Li,Lei; Sun,Zuyue

doi:10.3892/etm.2020.8521

Oral exposure of sulpiride promotes the proliferation of Brown‑Norway rat prostates

Authors:
- Chengcheng Zheng
- Yongwei Luo
- Ying Chen
- Dingshi Chen
- Congcong Shao
- Dongyan Huang
- Jing Zhu
- Xiaoyan Mao
- Lei Li
- Zuyue Sun
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Affiliations: School of Pharmacy, Fudan University, Shanghai 200433, P.R. China, National Evaluation Centre for The Toxicology of Fertility Regulating Drugs, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, P.R. China
Published online on: February 11, 2020 https://doi.org/10.3892/etm.2020.8521
Pages: 2551-2562
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to establish an animal model of prostatic hyperplasia to explore the mechanisms of this disease. Sulpiride, a specific type 2 dopamine receptor antagonist, causes prostate toxicity by stimulating prolactin (PRL) production. Male Brown‑Norway (BN) rats were treated intragastrically (i.g.) with sulpiride (40 and 120 mg/kg daily) and vehicle (i.g., daily) for 4 weeks. The results demonstrated that sulpiride‑treatment resulted in increased prostate size, prostate lobe weight, epithelial height and acinar luminal area. Furthermore, prostate lobe weight, epithelial height and acinar luminal area of lateral lobes (LP) significantly increased. These effects were dose dependent. Sulpiride treatment increased serum PRL, follicle‑stimulating hormone and testosterone levels, while serum luteinizing hormone levels were reduced. Immunohistochemical analysis revealed that proliferating cell nuclear antigen and B‑cell lymphoma‑2 were significantly increased in certain sulpiride treated groups. Furthermore, estrogen receptor (ER)‑α and androgen receptors were upregulated, while ERβ was downregulated in LP. The expression of stromal cell biomarkers, including vimentin, fibronectin and α‑smooth muscle actin were significantly increased in LP following 40 mg/kg sulpiride administration. These results suggest that sulpiride causes LP hyperplasia in BN rats by promoting proliferation and inhibiting prostate cell apoptosis via ERα and AR signaling.

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