Our understanding of the neuroendocrine mechanisms that underlie reproductive senescence in humans is severely limited by the lack of an appropriate animal model in which to perform key experiments. Because adult female rhesus macaques (Macaca mulatta) show menstrual cycles that are essentially indistinguishable from those of women, they represent a potentially valuable animal model in which to examine the etiologies of human female reproductive disorders. However, it is currently unclear whether aging female rhesus macaques actually undergo menopause and show the precipitous decrease in circulating sex-steroid concentrations that is so characteristic of postmenopausal women. The proposed research will examine in detail the circulating endocrine profiles of twenty greater than 20 year-old female macaques to: 1) establish whether such a decrease does indeed occur and whether it is associated with a hyperelevation of circulating gonadotropin concentrations; 2) establish whether aging-associated changes in sex-steroid concentrations are associated with a dampening in the circadian release patterns of melatonin, cortisol, growth hormone and prolactin; 3) establish the exact sequence of these predicted endocrine changes in relation to the known aging-associated onset of impaired cognitive function and neuropathology (e.g., beta- amyloid plaque deposition). The investigation will be performed on conscious, unrestrained animals using a remote blood-sampling procedure that is well established in our laboratory; the menstrual cycles of these animals have been chronicled in detail for several years and suggest that approximately one third of them are likely to be already postmenopausal. This study is expected to firmly substantiate that menopause does occur in aged macaques and to characterize in detail the associated circadian changes in key neuroendocrine parameters. Moreover, it should help to identify the age at which menopause occurs in this animal model. Therefore, the proposed research will provide empirical endocrine data regarding the aging-associated changes in a non- human primate and, thereby set the stage for studies aimed at elucidating underlying casual mechanisms.
| Downs, Jodi L; Urbanski, Henryk F (2006) Neuroendocrine changes in the aging reproductive axis of female rhesus macaques (Macaca mulatta). Biol Reprod 75:539-46 |
| Gundlah, C; Kohama, S G; Mirkes, S J et al. (2000) Distribution of estrogen receptor beta (ERbeta) mRNA in hypothalamus, midbrain and temporal lobe of spayed macaque: continued expression with hormone replacement. Brain Res Mol Brain Res 76:191-204 |
