Dietary carotenoids may reduce testicular steroidogenesis through HMG‐CoA reductase in mice with altered carotenoid metabolism

Abstract

Higher serum levels of lycopene are inversely associated with prostate cancer incidence. Previous work in our lab has demonstrated that, in mice lacking carotene‐15,15′‐ monooxygenase (CMO1), dietary tomato powder or lycopene reduces testicular and serum testosterone levels. We hypothesized that lycopene may reduce testicular steroidogenesis through HMG‐CoA reductase (HMGCoAr). Nine‐ to twelve‐week‐old male wild‐type (WT), CMO1−/−, and carotene‐9′,10′‐monooxygenase knockout (CMO2−/−) mice were fed AIN‐93G‐based diets containing 10% tomato powder (TP), lycopene beadlets matched for lycopene content (LYC), or control diets for four days. We examined testicular mRNA and protein expression of canonical steroidogenic enzymes and found no alterations which explained the observed hormonal changes. However, protein levels of HMGCoAr were significantly decreased (p<0.05) in WT and CMO1−/− mice fed TP or LYC, but not in CMO2−/− mice. HMGCoAr mRNA expression was unaltered, suggesting that control is through a post‐transcriptional mechanism. We also examined mRNA expression of a testicular cholesterol acquisition mediator, SR‐B1, and found no changes. In summary, LYC and TP decreased testicular HMGCoAr protein levels in a CMO2‐ dependent manner, suggesting that metabolites of lycopene or other tomato carotenoids, produced by CMO2 cleavage, may mediate this effect.Grant Funding Source: NIH grant PHS‐1‐RO1 CA125384