Effect of dehydroepiandrosterone on cell growth and mitochondrial function in TM-3 cells.

Dehydroepiandrosterone (DHEA), a major steroid hormone, decreases with age, and this reduction has been shown to be associated with physical health. In the present study, the effect of DHEA on cell growth and mitochondrial function was investigated using TM-3 cells, a Leydig cell line. The growth of TM-3 cells exposed to 100 μM DHEA for 24h was inhibited due to cell cycle arrest, primarily in the S and G2/M phases, and this effect was caused by decreased activity of glucose-6-phosphate dehydrogenase (G6PD) and reduced expression of cyclinA and cyclinB mRNA. A novel finding was that DHEA improved TM-3 cell viability in a markedly time-dependent manner. Although no differences were observed in the configuration or number of TM-3 cell mitochondria following DHEA treatment, mitochondrial membrane permeability and the activity of succinate dehydrogenase (SDH) increased subsequent to 24h treatment of cells with 100 μM DHEA. Overall, the data demonstrate that DHEA inhibited TM-3 cell growth by decreasing G6PD activity and the expression of cyclin mRNAs, whereas it improved TM-3 cell viability by increasing mitochondrial membrane permeability and the activity of SDH. This could be one of mechanisms of DHEA exerts its biological function.