The Wnt/β-catenin signaling pathway controls several biological processes throughout development and adult life. Dysregulation of Wnt/β-catenin signaling underlies a wide range of pathologies in animals and humans, including cancer in different tissues. In this review, we provide an update of the Wnt/β-catenin signaling pathway and the possible roles of the Wnt/β-catenin signaling in the biology of testis, epididymis and prostate. Data from our laboratory suggest the involvement of 17β-estradiol and estrogen receptors (ERs) on the regulation of β-catenin expression in rat Sertoli cells. We also provide emerging evidences of the involvement of Wnt/β-catenin pathway in testis and prostate cancer. Our understanding of the role of Wnt/β-Catenin signaling in male reproductive tissues is still evolving, and several questions are open to be addressed in the future.
Expression of the estrogen receptor ESR1 is higher in the corpus than it is in the initial segment/caput and cauda of the epididymis. ESR1 immunostaining in the corpus has been localized not only in the nuclei but also in the cytoplasm and apical membrane, which indicates that ESR1 plays a role in membrane-initiated signaling. The present study investigated whether ESR1 mediates the activation of rapid signaling pathways by estradiol (E 2 ) in the epididymis. We investigated the effect of E 2 and the ESR1-selective agonist (4,4 0 ,4 0 0 -(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) on the activation of extracellular signal-regulated protein kinases (ERK1/2), CREB protein, and ETS oncogene-related protein (ELK1). Treatment with PPT did not affect ERK1/2 phosphorylation in the cauda, but it rapidly increased ERK1/2 phosphorylation in the initial segment/caput and corpus of the epididymis. PPT also activated CREB and ELK1 in the corpus of the epididymis. The PPT-induced phosphorylation of ERK1/2, CREB, and ELK1 was blocked by the ESR1-selective antagonist MPP and by pretreatment with a non-receptor tyrosine kinase SRC inhibitor, an EGFR kinase inhibitor, an MEK1/2 inhibitor, and a phosphatidylinositol-3-kinase inhibitor. In conclusion, these results indicate that the corpus, which is a region with high expression of the estrogen receptor ESR1, is a major target in the epididymis for the activation of rapid signaling by E 2 . The sequence of events that follow E 2 interaction with ESR1 includes the SRC-mediated transactivation of EGFR and the phosphorylation of ERK1/2, CREB, and ELK1. This rapid estrogen signaling may modulate gene expression in the corpus of the epididymis, and it may play a role in the dynamic microenvironment of the epididymal lumen.
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