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Calreticulin: an intracellular Ca++-binding protein abundantly expressed and regulated by androgen in prostatic
N Zhu1, E B Pewitt, X Cai
1Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Abstract:
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.
Insights
Calreticulin, an androgen-response gene, is regulated by androgens in the prostate. This suggests calreticulin may mediate androgen effects on intracellular calcium in prostate cells.
Area of Science:
- Endocrinology
- Molecular Biology
- Urology
Background:
- Androgens play a crucial role in the development and function of male reproductive organs.
- Identifying genes regulated by androgens is key to understanding prostate physiology and disease.
Purpose of the Study:
- To identify and characterize androgen-response genes in the rat ventral prostate.
- To investigate the role of calreticulin in androgen signaling within prostate epithelial cells.
Main Methods:
- Northern blot and Western blot analyses to assess gene and protein expression.
- Prostate organ culture to study gene induction.
- In situ hybridization and immunohistochemistry to determine protein localization.
Main Results:
- Calreticulin messenger RNA and protein levels are modulated by castration and androgen replacement in the rat prostate.
- Androgen regulation of calreticulin is specific to the prostate and seminal vesicles.
- Calreticulin is an intracellular protein in prostatic epithelial cells, suggesting a role in calcium homeostasis.
- Androgen regulation of calreticulin is conserved across rat, mouse, and human prostate tissues.
Conclusions:
- Calreticulin is a direct androgen-response gene in the prostate.
- Calreticulin is a potential mediator of androgen-regulated intracellular calcium signaling in prostatic epithelial cells.
- The findings highlight the conserved role of calreticulin in androgen-dependent prostate function.