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Endocrinology Vol. 139, No. 10 4337-4344
Copyright © 1998 by The Endocrine Society

ARTICLES

Calreticulin: An Intracellular Ca++-Binding Protein Abundantly Expressed and Regulated by Androgen in Prostatic Epithelial Cells1

Ning Zhu2, E. Bradley Pewitt3, Xiaoyan Cai, Evan B. Cohn, Sharon Lang, Robert Chen and Zhou Wang4

Department of Urology (N.Z., E.B.P., X.C., E.B.C., S.L., R.C., Z.W.) and Department of Molecular Pharmacology and Biological Chemistry (Z.W.), Northwestern University Medical School, Chicago, Illinois 60611

Address all correspondence and requests for reprints to: Zhou Wang, Department of Urology, Tarry 11–715, Northwestern University Medical School, Chicago, Illinois 60611. E-mail: wangz{at}nwu.edu

Calreticulin was identified in a screen for androgen-response genes in the rat ventral prostate. Northern blot and Western blot analyses in the rat model showed that both calreticulin messenger RNA and protein are down-regulated by castration and up-regulated by androgen replacement in the prostate. Northern blot analysis showed that calreticulin expression level in the prostate is much higher than that in seminal vesicles, heart, brain, muscle, kidney, and liver. The regulation of calreticulin expression by androgen is only observed in the prostate and seminal vesicles, two male secondary sex organs. The induction of calreticulin by androgen in prostate organ culture partially resists protein synthesis inhibition, suggesting that calreticulin is a direct androgen-response gene. In situ hybridization and immunohistochemistry studies showed that calreticulin is an intracellular protein in prostatic epithelial cells. Because calreticulin is a major intracellular Ca++-binding protein with 1 high-affinity and 25 low-affinity Ca++ binding sites, our observations suggest that calreticulin is a promising candidate that mediates androgen regulation of intracellular Ca++ levels and/or signals in prostatic epithelial cells. The expression of calreticulin is also regulated by androgen in the mouse and human prostate, suggesting that androgen regulation and function of calreticulin in the prostate are conserved evolutionarily.




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