The decline in testosterone biosynthesis during male aging: a consequence of multiple alterations

The decline in blood testosterone concentration during the course of male aging results in decreases in many physiological functions. However, the mechanism(s) responsible for this decline is not clear. Previous observations have suggested the involvement of multiple alterations or defects that inhibit the activities of proteins involved in steroidogenesis and result in reduced testosterone biosynthesis. Recent studies have demonstrated an age-related increase in cyclooxygenase-2 (COX2) activity and its tonic inhibition of steroidogenic acute regulatory gene expression and steroidogenesis in rat Leydig cells. These findings indicate the presence of a novel mechanism in male aging involving COX2 and suggest the potential application of COX2 inhibitors or other interventions in this mechanism to delay the decline in testosterone biosynthesis in aged males.