Contribution of mouse adrenal glands to intratumor androgens and growth of castration-resistant prostate cancer xenografts.

224Background: Historical studies using radioimmunoassay did not detect adrenal androgens in serum from castrate mice, and it is widely held that rodent adrenal glands do not make adrenal androgens due to lack of CYP17A expression. This contrasts with the clinical setting in which circulating adrenal androgens are significant and inhibition of adrenal CYP17A markedly decreases tissue androgens. Methods: We evaluated CYP17A (by methylation, transcript and protein) and androgens (by mass spectrometry) in adrenal glands of CB17-NOD/SCID mice. We determined the impact of adrenalectomy (ADX) on suppressing tumor androgens and growth in two patient derived xenografts (PDX) models of castration resistant prostate cancer (CRPC). Results: CYP17A is unmethylated, and transcript and protein are present in adrenals from intact and castrate mice. In castrate mice adrenal levels of DHEA (0.75 pg/mg), androstenedione (AED; 44pg/mg), T (12.5pg/mg) and DHT (4.7 pg/mg) are detectable and nearly 2 orders of magnitude higher...