Cyclooxygenase-2 and Reduced Steroidogenesis in the Aging Male

Extract

In rodents, as in men, there is age-related decline in serum levels of testosterone. Cohort studies in men have dissociated decline in testosterone from disease (1). Age-related changes in testosterone have significant potential public implications, including decline in sexual and muscle function and bone density (2, 3). As yet, testosterone hormonal therapy is not available for men.

Among the many rodent strains that have been studied, Brown Norway rats have proven to be particularly advantageous because of their long life span and because they rarely develop the tumors and excessive fat that typify other strains. Thus, in the Brown Norway rat strain as in men, aging effects can be disassociated from disease. Previous studies of these rats have shown that reduced testosterone biosynthesis by the Leydig cells, rather than loss of Leydig cells, explains age-related reductions in testosterone production (4). It has been shown that LH, the primary trophic stimulator of testosterone production by Leydig cells, does not decline significantly with age, although as in men there is diminished LH pulse amplitude (5). As yet, the molecular mechanism(s) by which reductions in testosterone occur largely are uncertain. Recent studies suggest the integral involvement of reduced cAMP in this process (6), but how cAMP is reduced is not known.