Could Testosterone Have a Therapeutic Role in Prostate Cancer?

To discuss the role of membrane androgen receptors and to investigate the potential role of testosterone-albumin conjugate in the prostate cancer (PCa) treatment. We identified studies published from 1990 onwards by searching the MEDLINE database of the National Library of Medicine. Initial search terms were “androgen receptors, cytoplasmic androgen receptor, and membrane androgen receptor” combined with “testosterone, testosterone-albumin conjugate, and prostate cancer treatment”. The androgen receptor plays a critical role in both development and progression of PCa. The latter is associated with changes in the androgen receptor axis and more precisely, with its conversion from a paracrine dependent signaling pathway for proliferation and survival of prostatic cells to an independent autocrine process. This malignant conversion is due to functional changes in which the androgen receptor activates not only normal genomic, but also novel non-genomic signaling pathways, which are not present in normal prostatic epithelial cells. Thus, treatments for neoadjuvant, adjuvant, and recurrent disease, all center on the regulation and manipulation of the androgen pathway. Recent discoveries however offer strong evidence of a direct apoptotic action induced by activation of the membrane androgen receptor by testosterone-albumin conjugates. Investigation of the molecular pathways of apoptosis through activation of the membrane androgen receptors in the androgen-independent PCa cell is important on the one hand because future manipulation of this mechanism can help with understanding and interpreting unknown to date characteristics of PCa and on the other hand, can contribute to the establishment of activators of membrane androgen receptors. In addition, study of the testosterone-albumin complex can constitute the basis for future treatments for PCa.