Androgen regulation of spermidine synthase expression in the rat prostate*Jomol Cyriac and Riffat Haleem contributed equally to this work.

Abstract

BACKGROUND Spermidine synthase, an essential enzyme in the polyamine synthesis pathway, was identified as one of the androgen-response genes in the rat ventral prostate. Characterization of androgen regulation of spermidine synthase is important to the understanding of androgenic regulation of polyamine synthesis. METHODS Full-length cDNA encoding rat spermidine synthase was isolated from a λZAP cDNA phage library. Young male adult Sprague-Dawley rats were used for castration and androgen replacement. Northern blot and in situ hybridization were used to characterize gene expression. RESULTS The amino acid sequence of rat spermidine synthase shares 99% and 94% identity with that of mouse and human spermidine synthase, respectively. Spermidine synthase gene is abundantly expressed and regulated by androgens in the ventral, dorsal, and lateral lobes of the rat prostate, and its expression is localized to the epithelial cells. Spermidine synthase also is regulated by androgens in the seminal vesicles but not in the muscle, brain, kidney, thymus, heart, or liver, suggesting that this enzyme is responsive to androgen in the male sex accessory organs only. The expression of spermidine synthase and two other enzymes involved in polyamine synthesis, S-adenosylmethionine decarboxylase and ornithine decarboxylase, are regulated by androgens coordinately. CONCLUSIONS Spermidine synthase is most abundantly expressed and regulated by androgens in the prostatic epithelial cells, suggesting that regulation of spermidine synthase is likely a key step in coordinated androgen regulation of polyamine synthesis in the prostate. Prostate 50: 252–261, 2002. © Wiley-Liss, Inc.