Abstract
During aging, the production of androgens by the testis Leydig cells gradually decreases. Phenolic compounds can improve testosterone biosynthesis and delay the onset of hypogonadal symptoms in males. In this study, sinapic acid phenethyl ester was evaluated for its ability to regulate gene expression and steroid production in Leydig cells. Specifically, the effects of this ester on the transcriptome of MA-10 Leydig cells were investigated by RNA-Seq. To better establish a structure-function relationship of the hydroxy-methoxyphenyl moiety of sinapic and phenethyl ester, its influences on gene expression were compared to those of its ferulic acid phenethyl ester analogue. According to the transcriptomic analysis, most genes encoding enzymes related to cholesterol biosynthesis are increased in response to sinapic acid phenethyl ester treatment of MA-10 Leydig cells. Interestingly, treatments with 10 μM of ferulic acid phenethyl ester increased cAMP-dependent Star promoter activation, gene expression and protein levels. In addition, treatments of MA-10 Leydig cells with 10 μM of sinapic or ferulic acid phenethyl ester resulted in increased progesterone production. Thus, our results indicate that sinapic and ferulic acid phenethyl esters can improve cholesterol and steroid biosynthesis in testicular Leydig cells.