Endocrine Abstracts

Gonadotropin-releasing hormone (GnRH) analogues are now the standard hormonal treatment for prostate cancer. A fundamental difference between GnRH agonist and antagonist treatment is the permanent suppression of both gonadotropins (LH and FSH) by antagonist, while a rebound in FSH is associated with agonist treatment. The benefits of antagonist include the immediate onset of action and profound long-term suppression of FSH, suggested to be an independent growth factor in prostate cancer. To determine the potential benefit of permanent FSH ablation in treatment of prostate cancer, we studied the effect of the GnRH antagonist degarelix, in the presence and absence of FSH supplementation, on androgen independent PC-3 human prostate cancer cell xenograft tumour growth in intact and gonadectomised nude mice.

Our experiments demonstrate that degarelix treatment suppresses tumour growth in both intact and gonadectomised nude mice compared to non-treated controls (P<0.0001), indicating that the effect is mediated by gonadotropins rather than androgen suppression. Degarelix also effectively suppressed LH and FSH in both groups of mice, and testosterone in intact mice. The observed suppression of PC-3 cell xenograft tumour growth by degarelix treatment was significantly inhibited by concomitant FSH treatment. Quantitative polymerase chain reaction demonstrated LHR and FSHR mRNA in the xenograft tumours, but not in cultured PC-3 cells. Hence, in vivo conditions are needed for gonadotropin receptor expression of PC-3 cells. In conclusion, we provide experimental evidence that FSH may function as a direct growth promoter of prostate cancer cells, suggesting that combined FSH and LH suppression by GnRH antagonist could offer an advantage over the isolated LH suppression achieved by GnRH agonist upon prostate cancer treatment.