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Naturally existing vitamin K consists of vitamins K1 and K2. Menaquinone‐4 (MK‐4), an analog of vitamin K2 and a product of vitamin K1 metabolism, can be detected in several organs, including the testis; however, the function of MK‐4 in these tissues has not been well characterized. Recent studies have suggested that vitamin K is involved in enhancing protein kinase A (PKA) activity in several cell types, thus regulating numerous PKA‐dependent biological processes. To highlight the effect of vitamin K, we focused on its role in the steroidogenic pathway. Experiments on vitamin K–deficient rats revealed a reduced expression of genes involved in the biosynthesis of cholesterol and steroid hormones in the testis. Moreover, compared with control animals, rats fed on MK‐4 diet presented significantly higher testosterone levels in the plasma and testis. These results suggest that vitamin K is involved in the steroidogenic pathway in the testis. Testosterone levels were found to increase in a dose‐dependent manner also in cell‐based experiments upon addition of MK‐4, but such an effect was not observed in vitamin K1 levels. Furthermore, the effect of MK‐4 on testosterone production was abolished by the specific PKA inhibitor H89, thus confirming the regulatory role of MK‐ 4 on PKA activation. Here, we describe how MK‐4 modulates PKA activation by enhancing intracellular 3′,5′‐cyclic adenosine monophosphate (cAMP) levels in testis‐ derived I‐10 cells. The presented evidence supports the role of MK‐4 in cAMP/PKA signaling and steroidogenesis.

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level