Age-associated gene expression changes in the arcuate nucleus of male rhesus macaques

Abstract

The hypothalamic arcuate nucleus (ARC) represents a major component of the neuroendocrine reproductive axis, and plays an important role in controlling the onset of puberty as well as age-associated reproductive senescence. Although significant gene expression changes have been observed in the ARC during sexual maturation it is unclear what changes occur during aging, especially in males. Therefore, in the present study we profiled the expression of reproduction-related genes in the ARC of young and old male rhesus macaques, as well as old males that had received 6 months of hormone supplementation (HS) in the form of daily testosterone and dehydroepiandrosterone; we also compared morning versus night ARC gene expression in the old males. Using Affymetrix gene microarrays, we found little evidence for age-associated expression changes for genes associated with the neuroendocrine reproductive axis, whereas using qRT-PCR we detected a similar age-associated decrease in PGR (progesterone receptor) that we previously observed in post-menopausal females. We also detected a sex-steroid-dependent and age-associated decrease in AR (androgen receptor) expression, with highest AR levels being expressed at night (i.e., coinciding with the natural peak in daily testosterone secretion. Finally, unlike previous observations made in females, we did not find a significant age-associated increase in KISS1 (Kisspeptin) or TAC3 (Neurokinin B) expression in the ARC of males, most likely because the attenuation of circulating sex-steroid levels in the males was much less than that in postmenopausal females. Taken together, the data highlight some similarities and differences in ARC gene expression between aged male and female nonhuman primates.