Clusterin (SGP‐2) in epididymal luminal fluid and its association with epididymal spermatozoa in androgen‐deprived rats

Abstract

Clusterin is a heterodimeric glycoprotein synthesized and secreted by rat Sertoli cells and epididymal epithelium. The goal of this study was to determine the presence of clusterin in the luminal fluid of the cauda epididymides and its association with the membranes of developing spermatozoa in the presence and absence of androgen. We have previously demonstrated by two-dimensional (2-D) Western blot probing for clusterin that in epididymal fluid the amounts of clusterin were: caput greater than corpus greater than cauda. Luminal fluid from cauda epididymides was collected from control and orchiectomized rats (6 and 12 days) and orchiectomized animals that received testosterone implants. Equal volumes of fluid were analyzed by 2-D Western blot probing for clusterin. Following orchiectomy, there was an increase in clusterin in the luminal fluid after 6 days and maximal amount after 12 days compared with control cauda fluid. Orchiectomized animals which received testosterone treatment showed levels of clusterin comparable to that of controls. Serum clusterin was detected in fluid of orchiectomized animals with and without testosterone. Western blots of cauda sperm membrane extracts of control animals and orchiectomized animals treated with testosterone had a very low level of epididymal clusterin, whereas extracts collected from orchiectomized animals revealed high levels of clusterin. We suggest that, in the normal animal, clusterin is secreted into the lumen of the proximal epididymis where it binds to the sperm membrane. In the distal epididymis, clusterin dissociates from sperm and is processed (proteolysis/endocytosis). We hypothesize that, in the absence of androgen, the processing and regulation of clusterin is disrupted.

Acute Effect of Vasectomy on the Function of the Rat Epididymal Epithelium and Vas Deferens

“…No temporal changes after vasectomy were detected for either mRNA in any region of the epididymis. Consistent with previous studies, the highest levels of Crisp-1 mRNA were found in the corpus and cauda epididymis and for clusterin in the caput epididymis (Cyr and Robaire, 1992;Mattmueller and Hinton, 1992;Roberts et al, 2001).…”

“…by Sertoli cells in the testis and is a major secretory protein of caput epididymis epithelial cells (Sylvester et al, 1984;Mattmueller and Hinton, 1992). Clusterin has been implicated in cell adhesion and aggregation (Silkensen et al, 1999), lipid transport (Burkey et al, 1992), and cell apoptosis (Buttyan et al, 1989).…”

Identification and Validation of Novel Androgen-Regulated Genes in Prostate Cancer

“…TRPM2, or Clusterin, also found in cluster (6,6), is another gene previously hypothesized to be androgen regulated. Mattmueller and Hinton (39) found that the caudal fluid of orchiectomized rats contain increased amounts of Clusterin, compared with control animals. Several kinases such as PCTAIRE-1 and cyclindependent kinase (CDK)-8, which in general are known to play key roles in cell cycle regulation and cell differentiation and have often been targeted for cancer therapy, were also found in this cluster.…”

Epididymal epithelium: Its contribution to the formation of a luminal fluid microenvironment

“…This association persists until sperm reach the cauda where clusterin dissociates from sperm, perhaps due to proteolytic processing, and is endocytosed by the epididymal epithelium (Hermo et al, 1991;Mattmueller and Hinton, 1991). Clusterin concentrations in cauda fluid increase following orchiectomy suggesting that the secretion, sperm association and processing of clusterin requires androgens (Mattmueller and Hinton, 1992). Many different functions have been proposed for clusterin including involvement in lipid transport, based on nucleotide similarity to apolipoprotein J (de Silva et al, 1990) and putative roles in programmed cell death (Brandyk et al, 1990).…”