A role for BCMO1 beyond carotenoid metabolism: regulation of androgen status and signaling (645.4)

Abstract

In human studies, higher serum lycopene (Lyc) levels are inversely associated with risk of prostate cancer (PCa), which is driven by androgens. Genomic alterations in carotene‐15,15’‐monooxygenase (BCMO1), which cleaves provitamin A carotenoids to yield retinal, have been shown to alter Lyc accumulation. We hypothesized that Lyc and tomato powder (TP) feeding may impact the prostate by altering testosterone (T) action and that BCMO1 may modulate this process. Nine‐ to fourteen‐week‐old male WT and Bcmo1‐/‐ mice were fed AIN‐93G‐based control or diets containing TP or Lyc for four days. Surprisingly, we found that independent of Lyc or TP feeding, loss of Bcmo1 decreased testicular esterified cholesterol (p<0.05) and testicular mRNA expression of 17β‐hydroxysteroid dehydrogenase 3 (p<0.001), which converts androstenedione to T. In parallel, Bcmo1‐/‐ mice show reduced serum T and reduced androgen receptor‐mediated gene expression in the prostate. Regardless of diet, the weight of the prostate and the seminal vesicles was correlated (R2=0.12, p=0.0015, and R2=0.33, p<0.0001, respectively) with logarithmic concentrations of serum T, in agreement with published androgen‐driven growth kinetics. In summary, BCMO1 seems to play a significant role in androgen and prostate physiology independent of its function in carotenoid metabolism, highlighting a potential role in PCa.Grant Funding Source: Supported by NIH grant PHS‐1‐RO1 CA125384