Leydig cell development and aging in the brown norway rat: Mechanisms and consequences

Hypogonadism affects about 5 million American men and is associated with reduced lean body mass, bone mineral density, muscle mass, and libido. As in men, serum testosterone (T) declines in Brown Norway rats as a consequence of reduced Leydig cell T production in response to luteinizing hormone (LH) rather than from reduced LH. Reduced T is associated with reductions in Leydig cell cyclic adenosine monophosphate production, cholesterol transfer from intracellular sources into the mitochondria (the rate-determining step in T formation), and downstream steroidogenic enzymes. There is strong evidence for the involvement of altered balance between reactive oxygen production and the antioxidant defense system in age-related T reduction. These findings suggest that manipulation of the Leydig cell redox environment and/or the stimulation of cholesterol transfer into mitochondria may represent novel targets for the prevention or treatment of age-related reductions in T.