Calorie restriction (CR) has been established as the only non-geneticmethod of altering longevity and attenuating biological changes associated withaging. This nutritional paradigm has been effective in nematodes, flies, rodents,dogs and possibly non-human primates. Its long history notwithstanding, little isknown regarding the exact mechanism(s) of CR action or its potential impact onthe hypothalamic-pituitary-gonadal (HPG) axis. The objectives of this projectwere to: 1) analyze neuroendocrine changes to the HPG axis that occur withaging and 2) evaluate the effects of moderate CR on reproductive function inmale rhesus macaques.

Pituitary gene expression profiling, semi-quantitative RT-PCR (sqRT-PCR)and immunohistochemistry showed circadian clock mechanism componentspresent in three age categories of macaques, demonstrated age differences inexpression for Per2, indicated differential expression of Per2 and Bmal1 atopposing time points and revealed daily rhythmic expression of REV-ERBαprotein. These data indicate the ability of the macaque pituitary to express coreclockgenes, their protein products, and to do so in a 24-hour rhythm.Young Adult CON and CR pituitary gene expression profiles detectedpotential differential expression in <150 probesets. A decline in TSHR and CGAwas detected in CR macaques as measured by sqRT-PCR.

Other genesinvestigated showed no diet-induced changes.Young Adult CON and CR testicular gene expression profiles detectedpotential differential expression in <300 probesets although mRNA expressionwas not altered based on sqRT-PCR and real-time RT-PCR. Age-related and/ordiet-induced changes in HSD17β3, INSL3, CSNK1E and CGA were observed ina separate experiment with CGA in Old Adult CR subjects returning to youthfullevels.Semen samples were collected from Young Adult CON and CRmacaques. Normal spermiogram measures, ZP-binding, AR assay and SCSA®were conducted and indicated no differences between CON and CR-treatedanimals. Both groups exhibited similar daily testosterone profiles with nodifferences in mean or maximum levels; however, daily minimum testosteronelevels were lower in CON animals.It appears that moderate CR had limited impact on neuroendocrine orreproductive function in male rhesus macaques based on our selected endpoints.Thus, advantageous CR health benefits can be achieved without obviousnegative consequences to the HPG axis.

http://drum.lib.umd.edu/bitstream/1903/6819/1/umi-umd-4307.pdf