In aging males, androgen production by testicular Leydig cells decreases at a rate of approximately 1% per year. Phenolic compounds may enhance testosterone biosynthesis and delay the onset of male hypogonadism. Gigantol is a bibenzyl compound isolated from several types of orchids of the genus Dendrobium. This compound has various biological activities, including antioxidant activity. However, its capacity to regulate gene expression and steroid production in testicular Leydig cells has never been evaluated. We investigated the effect of gigantol on MA-10 Leydig cells’ gene expression using an RNA-Seq approach. To further investigate the structure-function relationship of the hydroxy-methoxyphenyl moiety of gigantol, experiments were also performed with ferulic acid and isoferulic acid. According to transcriptomic analysis, all genes coding for cholesterol biosynthesis-related enzymes are increased in response to gigantol treatment, resulting in increased lipid droplets accumulation. Moreover, treatments with 10 μM gigantol increased StAR protein levels and progesterone production from MA-10 Leydig cells. However, neither ferulic acid nor isoferulic acid influenced StAR protein synthesis and progesterone production in MA-10 Leydig cells. Thus, our findings indicate that gigantol improves cholesterol and steroid biosynthesis within testicular Leydig cells.
Gap junctions, mainly formed by Gja1 (Connexin43), play an essential role in the regulation of proliferation and differentiation of spermatogonia in the testis. Regulation of the abundance of Gja1 in spermatogonia involves various processes, including gene transcription, mRNA maturation, protein synthesis, post-translational modifications, plasma membrane integration and protein degradation. However, gene expression of Gja1 is abnormally decreased in most testicular germ cell tumors. Hence, a better understanding of the mechanisms of transcriptional regulation of Gja1 in spermatogonia is essential to understand how the loss of its expression occurs during the development of testicular cancer. As in other cell types, activator protein-1 (AP-1) transcription factors may be involved in such regulatory process. Thus, AP-1 members were overexpressed in GC-1 cells to assess their impact on Gja1 expression. We showed that Jun and Fosl2 cooperate to activate the Gja1 promoter in GC-1 cells. Furthermore, the recruitment of Jun to the proximal region (−153 to +46 bp) of the Gja1 promoter has been confirmed via chromatin immunoprecipitation. Protein kinase A and calcium-calmodulin protein kinase I also contribute to the activation of Gja1 expression by improving the cooperation between AP-1 factors. Therefore, the reduction in Gja1 expression in testicular germ cell tumors may involve a loss of cooperation between AP-1 factors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.