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Adrenomedullin Gene Is Abundantly Expressed and Directly Regulated by Androgen in the Rat Ventral Prostate¹

Department of Urology (E.B.P., R.H., Z.W.), Department of Molecular Pharmacology and Biological Chemistry (Z.W.), and The Robert H. Lurie Cancer Center (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, 303 East Chicago Avenue, Chicago, Illinois 60611-3009. E-mail: wangz{at}nwu.edu

A gene-expression screen, looking for androgen response genes in the rat ventral prostate, has identified adrenomedullin (AM), a 52-amino acid pluripotent peptide hormone, first isolated from pheochromocytoma. Northern blot analysis demonstrates that the level of expression in the prostate is reduced at least 25-fold by castration, with the majority of the decrease occurring in the first day, and that androgen replacement in seven-day castrated rats stimulates expression to supernormal levels, with the majority of the increase occurring within 14 h. The level of expression in the prostate is at least 50-fold higher than in the adrenal gland and cardiac atria, tissues previously reported to have the highest level of expression in the rat. In prostate organ culture, androgen was able to induce AM expression; and this induction resists protein synthesis inhibition, indicating that AM is a direct androgen response gene in the prostate. In situ hybridization of normal rat prostate tissue showed that AM expression is localized in the epithelial cells. Our analysis demonstrates that AM, a multifunctional peptide hormone, is abundantly expressed and directly regulated by androgen in the prostate epithelial cells. Thus, AM has the potential to play a crucial function in androgen action in the prostate.

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