Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue

Prostate cancer (PC) is both an age and androgen-dependent disease. Paradoxically, systemic levels of androgens decline with age as the risk of PC rises. While there is no correlation between systemic androgen levels and the risk of PC, systemic androgen levels do not reflect the levels of androgen in prostate tissue. In metastatic PC, changes in the androgen biosynthesis pathway during hormone therapy cause increased levels of androgens in cancer tissue and contribute to continued androgen receptor (AR) signaling. It is possible that similar changes occur in normal prostate tissue as androgens decline with age and that this contributes to tumorigenesis. We sought to determine if the rat prostate is able to maintain functional levels of androgens despite low serum testosterone (T). Rats were castrated and implanted with capsules to achieve castrate, normal, sub- and supra-physiological levels of T. After six weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. QRT-PCR was used to quantify expression of genes involved in the androgen/AR signaling axis. Despite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were very similar. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the rat prostate can maintain a functional level of androgens despite low serum T levels. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining functional androgen levels.