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

ABSTRACT

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

Keywords:

Steroidogenic acute regulatory protein (StAR protein), StART proteins, peripheral type benzodiazepine receptor (PBR), cholesterol metabolism, cholesterol binding proteins, cholesterol transport proteins.