Localization and Molecular Heterogeneity of Sulfated Glycoprotein-2 (Clusterin) among Ventral Prostate, Seminal Vesicle, Testis, and Epididymis of Rats1

Abstract

In the rat reproductive tract, sulfated glycoprotein 2 (SGP-2) is present in the ventral prostate, seminal vesicle, testis, and epididymis. In the ventral prostate, SGP-2 is associated with the process of programmed cell death, while in the testis and epididymis a role for SGP-2 in sperm maturation has been proposed. Available information suggests that there are both inter- and intra-organ variations in SGP-2 localization, molecular forms, and response to androgen ablation. In the present study, localization of SGP-2 within the ventral prostate, seminal vesicle, and epididymis was compared by immunohistochemistry. In the ventral prostate of intact rats, immunoreactive SGP-2 was confined to a discrete population of epithelial cells lining the proximal ducts. Epithelial cells in other regions of the ventral prostate did not stain for SGP-2. A similar staining pattern was observed for the seminal vesicle; a small population of SGP-2-expressing epithelial cells was found in epithelium that did not stain for SGP-2. The epididymis also demonstrated a non-uniform staining pattern. The caput displayed strong immunoperoxidase reaction over the apical membrane and stereocilia of all principal cells. Principal cells also showed variable degrees of cytoplasmic staining ranging from weak to strongly positive. The corpus and cauda showed a similar staining pattern. After castration, all epithelial cells in the ventral prostate and seminal vesicle became intensely positive for SGP-2 staining. In the caput and cauda epididymis there was an increase in the number of principal cells demonstrating strong intracellular staining for SGP-2. These results suggest that as observed previously in the regressing ventral prostate, increased intracellular SGP-2 staining may also be associated with the regressing epididymis and seminal vesicle. Differences in molecular forms of SGP-2 were investigated by two-dimensional Western and lectin blots. Molecular forms of SGP-2 differed between testis and epididymis but were similar between ventral prostate and seminal vesicle. Prostate and seminal vesicle forms of SGP-2 differed from those of both testis and epididymis. Analysis of terminal carbohydrate present on the various SGP-2 molecular forms also confirmed the existence of heterogeneity. These results demonstrate the presence of multiple molecular forms of SGP-2 in various organs of the male reproductive tract in rats and suggest a possible variation in functional activity and/or half-life of SGP-2 in these organs.

Proteomic Profiling of Regionalized Proteins in Rat Epididymis Indicates Consistency between Specialized Distribution and Protein Functions

“…Of these 28 proteins, 8 have been reported to have regionalized behavior within the epididymis, such as Gln synthetase 20 and clusterin. 21,22 Our results are highly accordant with the reports describing those proteins previously known to be regionalized (Table 1). In addition, our results are the first to reveal the regional distribution of four other previously identified epididymal proteins (Table 1).…”

Clusterin and LRP2 are critical components of the hypothalamic feeding regulatory pathway

“…Clusterin has been implicated in a number of biological processes, such as immune modulation, sperm maturation, lipid transportation, neurodegeneration and cancer cell survival [13][14][15][16][17] . Interestingly, clusterin has been identified as a plasma leptin-binding partner and has been shown to modulate leptin signalling in LepRbexpressing cell lines 18 .…”

Orchidectomy Induces a Wave of Apoptotic Cell Death in the Epididymis*

“…The fundamental concept of apoptosis implies the existence of an extracellular regulator of this process [32]. The regression of the rat ventral prostate after orchidectomy is known ta occur as a result of apoptotic cell death , and is induced by androgen withdrawal (26,27].…”

“…Certain organic molecules, such as L·camitine and a-aminoisobutyric acid are found to be absorbed from the lumen of the epididymis [30,31]; their uptake is time-dependent and saturable [30,31]. In 1965, Marquis and Fritz reported a high concentration of camitine in the epididymis [32]. Afterwards, this small molecule, which is proposed to be involved in the maturation of spermatozoa [30,[33][34][35], is confirmed not to be synthesized by the epididymis [36,37], or enter the epididymis directly from the testis, but to be taken up from the peripheral circulation against a concentration gradient [33,36].…”

“…Moore and Bedford [26] proteins, clusterin and cathepsin 0 that are reported to be increased in expression in the epididymis after orchidectomy [32][33][34]. Clusterin is a patent inhibitor of complement-mediated cytolysis [35,36]; the binding of clusterin to the sperm membrane prior ta ejaculation could help to protect sperm fram complement attack in the female reproductive tract [35,36].…”