Impact of Aging on Cholesterol Transport Protein Expression and Steroidogenesis in Rat Testicular Leydig Cells

摘要

The current studies indicate that Leydig cells from old (24-27-Mo) rats secreted significantly less cholesterol inresponse to stimulators, hCG, forskolin, or Bt2cAMP as compared to cells from young mature (5-Mo) animals. This deficiencywas reversed by incubation of cells with free diffusible hydroxycholesterols, indicating that age-related decline intestosterone secretion primarily results from the reduced availability of substrate cholesterol. Aging also significantly diminishedthe Leydig cell mRNA levels of StAR/StarD1, StarD2 and StarD4 both under basal conditions in response tohCG stimulation. Likewise, aging decreased the mRNA levels of PBR/TSPO. These changes correlated well with the reducedaccumulation of cholesterol in Leydig cell mitochondria from old animals. Our results suggest that aging causedimpaired expression of key cholesterol transport proteins, StAR/StarD1, StarD4 and PBR/TSPO that resulted in inefficientdelivery of cholesterol to and within the mitochondria, and subsequently reduced conversion of cholesterol topregnenolone and decreased testosterone production.