Physiopathological aspects of the Wnt/β-catenin signaling pathway in the male reproductive system

Abstract

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.

Keywords: AR; ER; Sertoli cells; Wnt/β-catenin; cancer; epididymis; prostate; testis.

Figure 1. A new Wnt/β-catenin signaling model based on the study from Li et al. (A) In the absence of Wnt protein (Off State), the destruction complex (Axin, GSK3, CK1, APC and Dvl) resides in the cytoplasm, where it binds, phosphorylates, and ubiquitinates β-catenin by β-TrCP. The proteasome recycles the complex by degrading β-catenin. (B) In the presence of Wnt (On State), this protein induces the association of the intact complex with phosphorylated LRP. After binding to LRP, the destruction complex stills captures and phosphorylates β-catenin, but ubiquitination by β-TrCP is blocked. Newly synthesized β-catenin accumulates (Adapted from Clevers and Nusse²).

Figure 2. Expression of β-catenin in a primary culture of Sertoli cells from 20-d-old rats. (A) Detection of β-catenin in Sertoli cells by immunofluorescence. Specific immunostaining for β-catenin using rabbit polyclonal antibody generated against the amino acid sequence 680–781 from the C-terminal of human β-catenin (red) under basal conditions (C, control) and after incubation with 17β-estradiol (E2, 0.1 nM) for 24 h. Negative control was performed using normal rabbit serum at the same dilution of the antibody. Nuclei were stained with 4’, 6-diamidino-2-phenylindole (blue). Bar = 100 µm. The data shown are representative of three independent experiments. (B) Detection of β-catenin in Sertoli cells by western blot. Cells were incubated in the absence (C, control) and presence of E2 (0.1 nM) for 6 and 24 h. Total cell lysates (40 µg protein/lane) were resolved on 7.5% SDS-PAGE. Immunoblotting using the anti-β-catenin antibody revealed specific bands (top panel) or with antibody that recognizes actin (bottom panel). The data shown are representative of six independent experiments. Bars represent the densitometric analysis of the western blot assays. Results were normalized to actin expression in each sample and plotted (mean ± SEM) in relation to control (C = 1). * β-catenin expression significantly different from control (p < 0.05, Student t-test).