Cyanidin-3-O-glucoside promotes the biosynthesis of progesterone through the protection of mitochondrial function in Pb-exposed rat leydig cells

Cyanidin-3-O-glucoside (C3G) is an anthocyanin that has been reported to reduce the toxicity of heavy metals. In the present study, the protection effects of C3G on the biosynthesis of progesterone, the precursor of testosterone, against lead (Pb) in R2C rat Leydig cells were examined. Treatment of R2C cells with 100 mu M Pb resulted in a significant decrease in progesterone production. After being cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in progesterone concentration compared with the Pb treatment, as a result of up regulation of the expression of the steroidogenic enzymes steroidogenic acute regulatory protein (StAR), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1). Pb-induced inhibition of extracellular regulated Kinase 1/2 (ERK 1/2) phosphorylation and down regulation of protein kinase A (PICA) expression were alleviated by C3G. In addition, Pb-induced reactive oxygen species (ROS) overproduction led to mitochondrial depolarization, resulting in a decrease in progesterone biosynthesis, while C3G intervention reduced the ROS level and increased progesterone production. In conclusion, C3G may alleviate the Pb-induced decrease of progesterone biosynthesis by modulating the dysfunction of mitochondria, including decreasing oxidative stress and regulating expression of steroidogenic enzyme proteins.