A Role for BCO1 Beyond Carotenoid Metabolism: Effects on Androgen Status and Prostatic Homeostasis

Abstract

In human studies, higher serum lycopene (Lyc) levels are inversely associated with risk of prostate cancer, which is driven by androgens. Genomic alterations in carotene‐15,15′‐monooxygenase (BCO1) have been shown to alter Lyc metabolism. However, potential functions of BCO1 beyond carotenoid cleavage are unknown. We hypothesized that Bco1 genotype would interact with dietary Lyc or tomato powder (TP) to alter murine androgen and prostatic biology. We conducted three separate studies in which 9‐ to 14‐week‐old male wild‐type (WT) and Bco1‐/‐ mice were fed AIN‐93G control or diets containing 10% TP or matched levels of Lyc for four days. Across all three studies, we found that Bco1 gene loss significantly (p<0.05) and consistently depressed androgen status and disrupted prostatic homeostasis – independently of Lyc or TP feeding. Loss of Bco1 decreased testicular mRNA expression of 17β‐hydroxysteroid dehydrogenase 3 ‐ a key enzyme in testosterone (T) synthesis ‐ by 29% and reduced serum T levels by 79%. Regardless of diet, the weight of the prostate was reduced by 14‐19% in Bco1‐/‐ mice compared to WT. In agreement with this, Bco1‐/‐ mice demonstrated reduced androgen signaling in the prostate (Msmb mRNA expression, ‐30%, Igfbp3 mRNA expression, +20%) as well as decreased mRNA expression of markers of cellular proliferation (Pcna, ‐12%; Ki67, ‐44%) and cell cycle entry into mitosis (Aurkb, ‐54%; Ccnb2, ‐51%). In summary, BCO1 seems to play a significant role in androgen and prostate physiology independent of its function in carotenoid metabolism.