抄録
Although most of the menaquinone analogues (MK-n = VK 2 ) are synthesized by microorganisms, we have reported that a unique synthesis of MK-4 occurs through the conversion of orally ingested VK 1 or MK-n in the major tissues of germfree rats and mice which lack their intestinal microbiota. Therefore, this study was undertaken to clarify the physiological role of MK-4 present in various tissues of the body. At first, the expression of genes in the liver and testis of rats was examined under vitamin K-deficient conditions using an exhaustive DNA microarray. Under vitamin K-deficient conditions, the liver showed an increase in the expression of genes involved in the acute inflammatory response and the testis showed a decrease in the expression of genes involved in the biosynthesis of cholesterol and steroid hormones. MK-4 was found to exert an anti-inflammatory action in the liver by suppressing the secretion of inflammatory cytokines. MK-4 suppressed the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of nuclear factor κB activation through the repression of IKK α ⁄ β phosphorylation. Rats fed a MK-4-supplemented diet for five weeks had significantly higher plasma and testis testosterone levels than control rats. The protein level of cholesterol side-chain cleavage enzyme (Cyp11a = P450scc), a limiting enzyme in the synthesis of steroids, especially sex hormones, in the testis was higher in the MK-4-supplemented group than in the control group. MK-4 was found to stimulate testosterone synthesis in vivo and in vitro . MK-4 played a novel role in stimulating testosterone synthesis in I-10 cells through regulation of cAMP⁄ PKA signaling pathway.
