An interaction between carotene-15,15′-monooxygenase expression and consumption of a tomato or lycopene-containing diet impacts serum and testicular testosterone

Lycopene, the red pigment of tomatoes, is hypothesized to reduce prostate cancer risk, a disease strongly dependent upon testosterone. In this study, mice lacking the expression of carotene-15,15′-monooxygenase (CMO-I ^-/-) or wild-type mice were fed either a 10% tomato powder (TP), lycopene-containing (248 nmol/g diet) or their respective control diets for 4 days, after which serum testosterone was measured. A significant diet × genotype interaction (p = 0.02) suggests that the TP reduces serum testosterone concentrations in CMO-I ^-/- mice but not in wild-type mice. Similarly, testicular testosterone was lowered in TP-fed CMO-I ^-/- mice (p = 0.01), suggesting that testosterone synthesis may be inhibited in this group. A similar pattern was also observed for lycopene fed mice. Interestingly, the CMO-I ^-/- mice showed a greater expression of the gene encoding the CMO-II enzyme responsible for eccentric oxidative carotenoid cleavage in the testes. Therefore, we hypothesize that serum testosterone is reduced by lycopene metabolic products of oxidative cleavage by CMO-II in the testes. Overall, these findings suggest that genetic polymorphisms impacting CMO-I expression and its interaction with CMO-II, coupled with variations in dietary lycopene, may modulate testosterone synthesis and serum concentrations. Furthermore, carefully controlled studies with tomato products and lycopene in genetically defined murine models may elucidate important diet × genetic interactions that may impact prostate cancer risk.