Pharmacia Award 1990. The biological significance of low testosterone levels and of adrenal androgens in transplantable prostate cancer lines.

The transplantable androgen-dependent human prostate tumor models PC-82 and PC-EW were used to study whether low levels of testosterone and androgens of adrenal origin were capable of stimulating the growth of prostatic carcinoma cells in these tumor models. At all circulating plasma testosterone levels applied in this study, much lower levels of dihydrotestosterone were found in PC-EW tumor tissue than in PC-82 tumor tissue. Nevertheless, both prostate tumor models had a similar threshold level of dihydrotestosterone for growth stimulation, i.e. 3-4 pmol/g tissue. This critical androgen level for tumor growth amounted to 2-3 times the tissue level found in castrated animals. At this threshold level approximately 2% of the cells showed proliferative activity, as assessed by bromodeoxyuridine incorporation into DNA. The adrenal androgen dehydroepiandrosterone did not stimulate PC-82 tumor growth, whereas androstenedione did induce a moderate increase in tumor volume. It is concluded that the adrenal androgen androstenedione exerts a stimulating effect on prostatic cancer cells when its conversion results in intra-tissue testosterone and dihydrotestosterone levels exceeding the threshold level for tumor growth.