Testosterone Measurement in Patients with Prostate Cancer Claude C. Schulman, Jacques Irani, Juan Morote, Jack A. Schalken, Francesco Montorsi, Piotr L. Chlosta, Axel Heidenreich  European Urology  Volume 58, Issue 1, Pages 65-74 (July 2010) DOI: 10.1016/j.eururo.2010.04.001 Copyright © 2010 European Association of Urology Terms and Conditions

Fig. 1 Classical and backdoor pathways of steroidogenesis. Reproduced with permission from John Wiley & Sons Inc. [6]. 5-AR1,2=5α-reductase-1,2; AKR1C1,2,3=aldo-keto reductase family 1, member C-1,2,3; DHEA=dehydroepiandrosterone; CYP11A1=cytochrome P450, family 11, subfamily A, polypeptide 1; CYP17A=cytochrome P450 17α-hydroxylase; HSD3B2=3β-hydroxysteroid dehydrogenase-2; HSD17B=17β-hydroxysteroid dehydrogenase. European Urology 2010 58, 65-74DOI: (10.1016/j.eururo.2010.04.001) Copyright © 2010 European Association of Urology Terms and Conditions

Fig. 2 Mechanisms of castration resistance in prostate cancer (PCa). Reproduced with permission from the Massachusetts Medical Society [21]. During androgen-dependent progression, PCa cells depend primarily on the androgen receptor (AR) for growth and survival. When the AR is inactive, it is bound to heat shock proteins (HSP) in the cytoplasm of prostate cells. The androgen dihydrotestosterone (DHT) binds to the AR, dissociating it from HSPs. The DHT-bound AR translocates into the nucleus, dimerizes, and binds to the androgen-response elements, thereby activating genes involved in cell growth. During androgen-independent progression, PCa relies on various cellular pathways, some involving the AR and others bypassing it. In the former type of pathway, a mutated AR may be activated by various ligands. In addition, deregulated growth factors and cytokines can activate the AR, usually with the help of AR coactivators. The AR may be amplified and therefore activated by reduced levels of DHT. In the pathways that bypass the AR, the loss of PTEN reverses the inhibition of the phosphatidylinositol 3-kinase/Akt pathway, permitting activated Akt to phosphorylate Bad. This activation results in the release of Bcl2, which eventually leads to cell survival. In addition, androgen-independent cells may overexpress Bcl2. PCa cells may develop neuroendocrinelike behaviour. Neuroendocrine cells secrete neuropeptides that induce the growth of adjacent cells, and thus PCa may survive therapeutic interventions. European Urology 2010 58, 65-74DOI: (10.1016/j.eururo.2010.04.001) Copyright © 2010 European Association of Urology Terms and Conditions

Fig. 3 Expression of androgen receptor (AR) in benign prostatic hyperplasia (BPH; left panel) and recurrent prostate cancer (right panel), with AR immunostaining shown in brown. Reproduced with permission from John Wiley & Sons Inc. [8]. European Urology 2010 58, 65-74DOI: (10.1016/j.eururo.2010.04.001) Copyright © 2010 European Association of Urology Terms and Conditions