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Articles

Testosterone and Food Restriction Modulate Hepatic Lycopene Isomer Concentrations in Male F344 Rats¹

Thomas W.-M. Boileau^*, Steven K. Clinton, Susan Zaripheh^*, Marcia H. Monaco^*, Sharon M. Donovan^* and John W. Erdman, Jr.^*2

^* Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Division of Hematology and Oncology, The Ohio State University, Columbus, Ohio 43210

²To whom correspondence should be addressed at University of Illinois, 449 Bevier Hall, 905 S. Goodwin Avenue, Urbana, IL 61801. E-mail: j-erdman{at}uiuc.edu

We previously demonstrated that the castration of male rats profoundly increases hepatic lycopene compared with intact controls. Here we further characterized the role of testosterone in modulating hepatic lycopene accumulation and isomer patterns in male rats. Furthermore, because castration significantly decreases ad libitum food consumption, we investigated the influence of food restriction on lycopene metabolism. Forty male F344 rats 8 wk of age were randomly assigned to one of four treatments (n = 10/group): 1) intact, free access to food, 2) castration, free access to food, 3) castration plus testosterone implants, free access to food and 4) intact, 20% food restricted. All rats were fed an AIN-based diet with 0.25 g lycopene (as 10% water-soluble beadlets)/kg diet for 3 wk. Serum testosterone was 5.31 ± 1.46 nmol/L in intact controls allowed free access to food, reduced in castrated animals (0.52 ± 0.10, P < 0.0001 versus controls) and intact, food-restricted rats (1.53 ± 0.49 nmol/L, P < 0.0001 versus controls) and greater (17.23 ± 3.09 nmol/L) in castrated rats administered testosterone (P < 0.0001 versus controls). Castrated rats accumulated approximately twice as much liver lycopene (74.5 ± 8.5 nmol/g; P < 0.01 versus controls) as intact rats allowed free access to food (39.5 ± 5.0) despite 13% lower dietary lycopene intake (P < 0.001; 3.38 ± 0.07 versus 3.95 ± 0.06 mg lycopene/d). Testosterone replacement in castrated rats returned liver lycopene concentrations (32.5 ± 5.5 nmol lycopene/g with 3.76 ± 0.05 mg dietary lycopene/d) to those observed in intact rats. Food restriction resulted in a 20% decrease in lycopene intake but significantly increased liver lycopene by 68% (66.3 ± 7.9 nmol lycopene/g with 3.38 ± 0.00 mg lycopene/d) compared with controls and castrated rats administered testosterone. These results suggest that androgen depletion and 20% food restriction increase hepatic lycopene accumulation. We hypothesize an endocrine and dietary interaction, where higher androgen concentrations and greater energy intake may stimulate lycopene metabolism and degradation.

KEY WORDS: • lycopene • testosterone • prostate cancer • rats • antioxidants