Download or read book Mechanism of Androgen Action in the Prostate written by Feng Jiang and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Androgens are required for the structural and functional integrity of the prostate. Androgen action is intimately involved in the pathogenesis of two major prostate diseases, benign prostatic hyperplasia (BPH) and prostate carcinoma (CaP). Androgens regulate gene expression in the prostate through the androgen receptor (AR), a ligand-dependent transcription factor. To understand the molecular and cellular mechanisms of androgen action in the prostate, I used both cDNA subtractive hybridizations and microarray to comprehensively identify genes regulated by androgens using the rat ventral prostate model. Twenty-two genes up-regulated by androgens were isolated from my subtraction studies. From my microarray study, 162 and 143 genes were found to be up-regulated and down-regulated by androgens, respectively. Identification of these genes suggests that the following pathways are activated by androgens in the prostate---metabolism, protein synthesis, protein chaperoning and trafficking, secretions, cell cycle and apoptosis, and structural and extracellular proteins. I have characterized four androgen-responsive genes: FPPS, PLZF, GADD45gamma, and U19. FPPS is abundantly expressed and regulated by androgens in the rat prostatic epithelial cells. Both PLZF and GADD45gamma are found to be growth-suppressive to prostate cancer cells, suggesting that androgens might activate a signaling pathway to counteract the androgen-induced cell proliferation pathway. U19, a novel androgen-responsive apoptosis inducer, is also growth-suppressive to prostate cancer. Therefore, U19 was chosen for further mechanistic study. I identified FBI as a protein partner for U19. I determined that FB1 also interacts with EAF1, PML and ELL, and FB1 inhibits the transcriptional activity of U19. In conclusion, my thesis established a foundation for future mechanistic study of androgen action and provided new insights into the roles played by androgens in the prostate.