Endocrinology, Vol 126, 2989-2997, Copyright © 1990 by Endocrine Society

ARTICLES

Diverse secretory patterns of clusterin by epididymis and prostate/seminal vesicles undergoing cell regression after orchiectomy

J Grima, I Zwain, RA Lockshin, CW Bardin and CY Cheng
Population Council, Center for Biomedical Research, New York, New York 10021.

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.

This article has been cited by other articles:

				M. Scaltriti, A. Santamaria, R. Paciucci, and S. Bettuzzi Intracellular Clusterin Induces G2-M Phase Arrest and Cell Death in PC-3 Prostate Cancer Cells1 Cancer Res., September 1, 2004; 64(17): 6174 - 6182. [Abstract] [Full Text] [PDF]

				C. Sorrentino,, B. Silvestrini,, L. Braghiroli,, S. S.W. Chung,, S. Giacomelli,, M.-G. Leone,, Y.-b. Xie,, Y.-p. Sui,, M.-y. Mo,, and C. Y. Cheng Rat Prostaglandin D2 Synthetase: Its Tissue Distribution, Changes during Maturation, and Regulation in the Testis and Epididymis Biol Reprod, October 1, 1998; 59(4): 843 - 853. [Abstract] [Full Text]

				J. Grima, C. C. S. Wong, L.-j. Zhu, S.-d. Zong, and C. Y. Cheng 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 J. Biol. Chem., August 14, 1998; 273(33): 21040 - 21053. [Abstract] [Full Text] [PDF]

				S.-M. Ho, I. Leav, S. Ghatak, F. Merk, V. S. Jagannathan, and K. Mallery Lack of Association between Enhanced TRPM-2/Clusterin Expression and Increased Apoptotic Activity in Sex-Hormone-Induced Prostatic Dysplasia of the Noble Rat Am. J. Pathol., July 1, 1998; 153(1): 131 - 139. [Abstract] [Full Text] [PDF]

				L.-J. Zhu, M. K. Bagchi, and I. C. Bagchi Attenuation of Calcitonin Gene Expression in Pregnant Rat Uterus Leads to a Block in Embryonic Implantation Endocrinology, January 1, 1998; 139(1): 330 - 339. [Abstract] [Full Text] [PDF]

				G. R. Aravindan, D. Mruk, W. M. Lee, and C. Y. Cheng Identification, Isolation, and Characterization of a 41-Kilodalton Protein from Rat Germ Cell-Conditioned Medium Exhibiting Concentration-Dependent Dual Biological Activities Endocrinology, August 1, 1997; 138(8): 3259 - 3268. [Abstract] [Full Text] [PDF]

				A. Hurwitz, K. Ruutiainen-Altman, L. Marzella, L. Botero, M. Dushnik, and E. Y. Adashi Follicular Atresia as an Apoptotic Process: Atresia-Associated Increase in the Ovarian Expression of the Putative Apoptotic Marker Sulfated Glycoprotein-2 Reproductive Sciences, July 1, 1996; 3(4): 199 - 208. [Abstract] [PDF]