Adrenomedullin gene is abundantly expressed and directly regulated by androgen in the rat ventral prostate

A gene-expression screen, looking for androgen response genes in the rat ve ntral prostate, has identified adrenomedullin (AM), a 52-amino acid pluripo tent peptide hormone, first isolated from pheochromocytoma. Northern blot a nalysis demonstrates that the level of expression in the prostate is reduce d at least 25-fold by castration, with the majority of the decrease occurri ng in the first day, and that androgen replacement in seven-day castrated r ats stimulates expression to supernormal levels, with the majority of the i ncrease occurring within 14 h. The level of expression in the prostate is a t 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 thi s induction resists protein synthesis inhibition, indicating that AM is a d irect androgen response gene in the prostate. In situ hybridization of norm al rat prostate tissue! showed that AM expression is localized in the epith elial cells. Our analysis demonstrates that AM, a multifunctional peptide h ormone, is abundantly expressed and directly regulated by androgen in the p rostate epithelial cells. Thus, AM has the potential to play a crucial func tion in androgen action in the prostate.