Endocrine Abstracts

It has been established in recent years that androgens are involved in the progression of castration resistant prostate cancer (CRPC). Although androgen deprivation therapy reduces the level of androgens and inhibits the androgen receptor, there are studies reporting that the androgen signaling axis is still involved in the development of CRPC. We have in a previous study shown that low level of β₂-adrenergic receptor (ADRB2) is associated with shorter time to CRPC in a patient cohort. One possible mechanism is the role of ADRB2 in regulating the level of glucuronidation of androgens in prostate cancer cells, altering the levels of steroids in favour of development of CRPC. In this study, we determined the steroid profile in tissue and serum samples from LNCaP xenograft models expressing high or low levels of ADRB2. Using a multi-steroid LC-MS/MS assay the levels of testosterone, dihydrotestestoren, progesterone and aldosterone were measured. Serum samples were taken at the day of castration and weekly up until termination. Tumor samples were homogenized to extract steroids for determination of the intratumoral concentration. The intratumoral cholesterol level was also measured, as this is an important precursor in the androgen synthesis. PSA was measured to follow the progression of the development of CRPC in the xenograft mice after castration. The results from our analysis indicated that the intratumoral levels of dihydrotestosterone, progesterone and aldosterone were increased in xenograft tumors with low level of ADRB2. The level of total cholesterol was also higher in xenograft tumors with low expression of ADRB2. The steroid profile from serum samples showed no difference in the levels of the measured steroids at the day of castration. We observed a decrease in serum levels of androgens in the time course analysis for both groups. Whereas the level of progesterone showed an initial increase after castration, followed by decreasing levels three weeks post castration.

Presenting author: Håkon Ramberg, Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Ullerenchausseen 70 0379 Oslo, Norway. Email: [email protected].