Diverse Secretory Patterns of Clusterin by Epididymis and Prostate/Seminal Vesicles Undergoing Cell Regression after Orchiectomy*

Abstract

Nucleotide sequence analysis of the complimentary DNAs (cDNA) and N-terminal amino acid sequence analysis have shown that clusterin is equivalent to sulfated glycoprotein-2 (SGP-2), testosterone-repressed prostate protein-2 (TRPP-2), and androgen-repressed protein (ARP) in the rat, as well as serum/seminal plasma protein, SP-40,40, in the human. In view of its widespread presence in various species, a specific RIA was established to quantify the tissue distribution of this protein. Rat clusterin is present in almost all organ tissues examined, including testis, epididymis, serum, liver, prostate, seminal vesicles, and uterus. Displacement curves generated using cytosols prepared from these organs were parallel to those obtained using purified rat clusterin and crude Sertoli cell-enriched culture medium. Immunoreactive clusterin was also visualized in these organ extracts by immunoblots. Studies on the tissue distribution of immunoreactive clusterin using RIA revealed that the concentration of clusterin in the epididymis of adult rats was 6- and 10-fold higher than that in the serum and testis, respectively and is 50- to 100-fold higher in the liver, spleen, kidney, brain, ventral prostate, seminal vesicles, and uterus. A study of the distribution of clusterin in various compartments of the epididymis indicated its concentration in the caput epididymis was almost 3-fold higher than that in the corpus and cauda epididymis. After orchiectomy, the concentrations of clusterin in the ventral prostate and seminal vesicles increased as much as 100- and 10-fold and peaked at day 4 after surgery, respectively; daily injection of dihydrotestosterone (DHT) beginning at day 3 after orchiectomy reduced the concentrations of clusterin and restored them to a normal level. A different pattern was noted in the epididymis after orchiectomy; the concentration of clusterin in the caput epididymis decreased with time; however, daily injection of DHT beginning at day 3 increased the caput epididymal clusterin concentration and restored it to a normal level. The concentration of clusterin was not altered in the corpus or cauda epididymis after castration and/or DHT administration. Also, the serum and liver clusterin levels did not change with time after orchiectomy. These observations suggest that clusterin will be a valuable marker to monitor the diverse effects of androgen withdrawal in the male reproductive tract. We conclude that clusterin may be a multifunctional protein in view of its broad tissue distribution and association with numerous physiological and pathological conditions.

Accumulated HSV1-TK Proteins Interfere with Spermatogenesis through a Disruption of the Integrity of Sertoli-Germ Cell Junctions

“…On the other hand, the increased expression of growth factors, such as growth factor fgf7, osteoclast stimulating factor ostf1 and cell proliferation factor cnot7 [27], may be a stress response in the transgenic rat testes. Among these results, our focus was ontestin, which is localized near the Sertoli cell surface in the testis where Sertoli and germ cells interact [28,29].…”

Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus.

“…Recent work by several groups has shown increased clusterin expression in epithelial or nervous tissues known to be regressing as a consequence ofapoptosis (20)(21)(22)(23)(24)(25), suggesting that clusterin may either be directly involved in this type ofcell death or associated with the process oftissue remodeling and repair. Little is known about the expression of clusterin in the lymphoid system in which apoptosis is a frequent and prominent physiological event (29, 30).…”

“…The expression ofthe clusterin gene is highly increased during the involution ofcertain tissues in response to developmental stimuli, hormonal modulations, or injury. Indeed, clusterin (or species homologous) transcripts and/or protein have been localized for example in: regressing interdigital tissue of fetal rat limb buds (20), prostatic epithelial cells after castration (20)(21)(22)(23), renal collecting ducts and distal tubules after ureteral obstruction (20,24), and rat hippocampus after experimental deafferentiation (25). Furthermore, there is substantial evidence that cell death occurring during the involution of these tissues is apoptotic.…”

Testin Secreted by Sertoli Cells Is Associated with the Cell Surface, and Its Expression Correlates with the Disruption of Sertoli-Germ Cell Junctions but Not the Inter-Sertoli Tight Junction

“…RIAs for testin (2), androgen binding protein (16,27), clusterin (28), and ␣ 2 -macroglobulin (29) were performed as detailed in previous reports.…”