Ketoconazoleの前立腺癌成長抑制作用と睾丸,副腎Androgen産生に及ぼす影響

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Donryu male rats were implanted with the tumor in the ventral prostate at 40 days of age; and 9 days later, they were concurrently orchiectomized and started on ketoconazole (Keto) injection (5 or 10 mg/rat/day, s.c.). Twenty days later, the rats were decapitated. The rats were divided into the following treatment groups: 1. Intact, 2. Intact + Keto-10 (10 mg), 3. Implanted (Imp), 4. Imp + Keto-5 (5 mg), 5. Imp + Keto-10, 6. Imp + castrated (Cast), 7. Imp + Cast + Keto-5 and 8. Imp + Cast + Keto-10. Keto induced slight inhibition of tumor growth but coincident castration led to a significant decrease of tumor development. Keto or castration increased adrenal weight. Keto could not alter plasma androgen in intact rats, but enhanced it significantly in low androgen situations as in groups 3 and 6. Keto significantly lowered plasma corticosterone and acted to decrease testicular androgen in group 1 (Intact); and in contrast, Keto acted to increase significantly testicular androgen in group 3 (Imp). These results suggest that: (1) Keto has a direct action to decrease the tumor weight and enhanced androgen in implantation and (2) Keto acts to decrease adrenal steroidogenesis.
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