MONOMERIC AND OLIGOMERIC EPIDIDYMAL PROSAPOSIN. A PARADOXICAL RELATIONSHIPT REGULATED BY ANDROGENS VIA SORTILIN AND CATHEPSIN D.

CARVELLI L; ZYLA L; SOSA MA; MORALES CR

Quebec City

Simposio; 7th RQR (Réseau Québécois en Reproduction) Symposium; 2014

Réseau Québécois en Reproduction

Introduction: The epididymis is implicated in sperm maturation by remodeling the sperm plasma membrane. Lysosomal proteins secreted by the epididymal epithelium may play a role in this process. Here we analyzed the expression of prosaposin (PSAP), cathepsin D (catD), and sortilin in the cauda epididymis of intact and castrated rats, followed or not by testosterone replacement. PSAP is trafficked as monomers to the lysosomes or secreted as oligomers. CatD is secreted by the principal cells into the lumen of the epididymis probably associated with PSAP. Sortilin is a TGN-resident protein implicated in the lysosomal sorting of PSAP and catD. Methods and results: PSAP immunostaining was not affected by castration. However, immunoblotting showed that castration decreased monomeric PSAP and increased oligomeric PSAP. PSAP showed a supranuclear staining in the principal cells that spread over the entire apical cytoplasm after castration. Immunoblotting with anti-catD showed an increase in the expression and secretion of this protein due to castration, which was reversed by testosterone injection. Immunostaining showed a supranuclear localization of catD in the principal cells. The reaction was more intense in castrated animals. Immunoprecipitation demonstrated that secreted catD was increased and associated in part to PSAP. Both immunoblotting and immunostaining with anti-sortilin indicated that the expression of this protein decreased with castration and reversed by testosterone replacement. Discussion: Our results suggest that lower levels of sortilin induced by castration increased PSAP oligomerization. We hypothesize that PSAP oligomers associate to catD increasing its secretion.