Endocrine Abstracts

Men show an age-associated decline in 24-hour circulating testosterone levels, but the reason for this decline is unclear. To shed light on the possible cause we first established that male rhesus monkeys undergo a similar decline in testosterone with age. Testosterone from young adult (∼10 years) and old (∼26 years) unanaesthetized males was measured by RIA from blood samples collected remotely through a vascular catheter, every 30 minutes for 24 hours. In both young and old animals, plasma testosterone showed a robust circadian pattern, with a peak occurring at night and a nadir occurring in the middle of the day. As expected, the peak, nadir, and overall mean testosterone levels were all significantly lower (P<0.001) in the old animals than in the young animals. Next, to help elucidate a possible mechanism for this age-associated decline, we extracted RNA from testicular parenchyma of three immature (∼2 years), three young adult (∼6 years) and three old (∼25 years) animals, and subjected the samples to GeneChip microarray analysis (Affymetrix HG-U133A). The gene encoding 17-β hydroxysteroid? dehydrogenase 3 (17-β HSD) showed a significant (P<0.05) developmental increase, suggesting that this enzyme may play a key role in activating testosterone biosynthesis during puberty. In contrast, the gene encoding steroidogenic acute regulatory protein (StAR), a key regulatory enzyme for testosterone biosynthesis, showed a significant (P<0.05) age-related decrease, suggesting that it may contribute to the age-associated decline in circulating testosterone. Interestingly, the microarray analysis also revealed the expression of the following clock-mechanism genes in the testis: Clock, Bmal1, Per1, Per2, Cry1, Rev-Erbα, and CK1ε and showed that CK1∈ declined significantly (P<0.05) during old age. Taken together, these data emphasize the circadian pattern of testosterone secretion in a nonhuman primate species, and suggest that transcriptional changes within the testis may contribute to the age-associated attenuation of this endocrine rhythm.