CALRETICULIN - AN INTRACELLULAR CA-BINDING PROTEIN ABUNDANTLY EXPRESSED AND REGULATED BY ANDROGEN IN PROSTATIC EPITHELIAL-CELLS(+)

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 replacem ent in the prostate. Northern blot analysis showed that calreticulin e xpression level in the prostate is much higher than that in seminal ve sicles, heart, brain, muscle, kidney, and liver. The regulation of cal reticulin expression by androgen is only observed in the prostate and seminal vesicles, two male secondary sex organs. The induction of calr eticulin by androgen in prostate organ culture partially resists prote in synthesis inhibition, suggesting that calreticulin is a direct andr ogen-response gene. In situ hybridization and immunohistochemistry stu dies 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 candi date that mediates androgen regulation of intracellular Ca++ levels an d/or signals in prostatic epithelial cells. The expression of calretic ulin is also regulated by androgen in the mouse and human prostate, su ggesting that androgen regulation and function of calreticulin in the prostate are conserved evolutionarily.