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The prostaglandin synthases, COX-2 and L-PGDS, mediate prostate hyperplasia induced by low-dose bisphenol A

This study aimed to identify prostaglandin synthases (PGS) that mediate bisphenol A (BPA)-induced prostatic hyperplasia and explore their underlying mechanisms. In an in vivo study, male adult Sprague–Dawley rats were treated with different concentrations of BPA (10, 30, 90, or 270 μg/kg, i.g., dail...

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Detalles Bibliográficos
Autores principales: Wu, Shuangshuang, Huang, Dongyan, Su, Xin, Yan, Han, Ma, Aicui, Li, Lei, Wu, Jianhui, Sun, Zuyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403327/
https://www.ncbi.nlm.nih.gov/pubmed/32753632
http://dx.doi.org/10.1038/s41598-020-69809-y
Descripción
Sumario:This study aimed to identify prostaglandin synthases (PGS) that mediate bisphenol A (BPA)-induced prostatic hyperplasia and explore their underlying mechanisms. In an in vivo study, male adult Sprague–Dawley rats were treated with different concentrations of BPA (10, 30, 90, or 270 μg/kg, i.g., daily), or with vehicle for 4 weeks. Results revealed that low-dose BPA induced prostatic hyperplasia with increased PCNA/TUNEL ratio. It significantly upregulated the expression of cyclooxygenase-2 (COX-2) and NF-κB in the dorsolateral prostate (P < 0.05) and the expression of lipocalin-type prostaglandin D synthase (L-PGDS) in ventral prostate (P < 0.05). The level of estradiol (E(2))/testosterone (T) and expression of androgen receptor (AR) and estrogen receptor α (ERα) were also altered. In vitro studies showed that low-dose BPA (0.1–10 nM) promoted the proliferation of human prostate fibroblasts and epithelial cells, and significantly upregulated the expression of COX-2 and L-PGDS in the cells. The two types of cell proliferation induced by BPA were inhibited by COX-2 inhibitor (NS398) and L-PGDS inhibitor (AT56), with increased apoptosis level. These findings suggested that COX-2 and L-PGDS could mediate low-dose BPA-induced prostatic hyperplasia through pathways involved in cell proliferation and apoptosis, which might be related to the functions of ERα and AR. The role of COX-2/NF-κB pathway in dorsolateral prostate requires further research.