Atlas of dihydrotestosterone actions on the transcriptome of prostate in vivo

Abstract

Using serial analysis of gene expression (SAGE), we studied the transcriptomic changes in vivo by dihydrotestosterone (DHT) treatment in mice to better understand androgen effects in the prostate. Approximately 872,000 SAGE tags were isolated from intact and castrated (GDX) mice with and without DHT injection. GDX significantly altered 431 transcripts, including 110 transcripts restored by DHT, and 146 potentially new transcripts. Totally, 187 transcripts were significantly affected by DHT treatment, of which 124 were induced and 63 were repressed. Interestingly and consistent with the prostate's secretory role, DHT up-regulated the expression of many genes involved in various steps of protein metabolism such as synthesis, folding, and secretion. GDX modulated the expression of genes which induce cell apoptosis and inhibit cell proliferation through polyamine biosynthesis, retinoid X receptor actions as well as several signaling pathways and some related factors. These results clarify DHT effects on prostate transcriptome in the areas of protein metabolism, cell proliferation and apoptosis. In addition, we detected gene expression changes in metabolic pathways, cytoskeleton, immunity and endoplasmic reticulum stress. Furthermore, knockdown of S-adenosylmethionine decarboxylase 1 in LNCaP cells confirmed the importance of androgen-regulated genes (ARGs) in prostate cancer cell growth. Our data support the idea that ARGs are essential for the normal development of the prostate and can also be responsible for the pathogenesis of the prostate cancer.