title: Impact of Moderate Calorie Restriction on the Reproductive Neuroendocrine Axis of Male Rhesus Macaques.
abstract: The impact of moderate calorie restriction on reproductive neuroendocrine function was investigated in young adult male rhesus macaques (Macaca mulatta). The animals were subjected to either 30% calorie restriction (CR; n=5), or were fed a standard control diet (CON; n=5), starting during their peripubertal period. Plasma LH and testosterone concentrations were examined after 7 years of differential dietary treatment, and were found to be similar in both groups, both during the day and during the night. Microarray profiling of pituitary gland and testicular gene expression was performed after 8 years of treatment, using GeneChip® Rhesus Macaque Genome Arrays (Affymetrix), and showed very little effect of caloric restriction. Using a 1.5-fold difference threshold, our microarray analysis revealed differential expression of only 145 probesets in the pituitary gland and 260 in the testes, out of a total of >54,000. Semi-quantitative RT-PCR performed on pituitary gland mRNA corroborated the microarray findings for selected modulated genes, including TSH receptor (TSHR) and sperm-specific antigen 2 (SSFA2). Most notably, significantly lower expression of TSH receptor mRNA was observed in the pituitary of CR compared to CON animals. Also, significantly lower expression of the glycoprotein hormone alpha subunit (CGA) was observed in CR animals, and this finding was further corroborated using quantitative real-time RT-PCR. No significant diet-induced changes were detected in the testis for genes associated with reproduction, circadian clocks, or oxidative stress. There is mounting evidence that CR may promote health and longevity in a wide range of organisms, including nonhuman primates. Importantly, our data suggest that moderate CR has no obvious lasting detrimental effect on the reproductive neuroendocrine axis of long-lived primates, and has only a modest influence on pituitary and testicular gene expression.
authors.affiliation: Department of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Sitzmann
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mattison
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.forename: George S
authors.initials: GS
authors.lastname: Roth
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Ottinger
authors.forename: Henryk F
authors.initials: HF
authors.lastname: Urbanski
references.citation: Aging Cell. 2004 Feb;3(1):7-12
references.pmid: 14965349
references.citation: Biostatistics. 2003 Apr;4(2):249-64
references.pmid: 12925520
references.citation: J Clin Endocrinol Metab. 2001 Feb;86(2):724-31
references.pmid: 11158037
references.citation: Toxicol Sci. 1999 Dec;52(2 Suppl):41-8
references.pmid: 10630589
references.citation: Endocrinology. 1998 May;139(5):2284-6
references.pmid: 9564835
references.citation: J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):B98-107
references.pmid: 11253152
references.citation: Brain Res. 1997 Jan 2;744(1):96-104
references.pmid: 9030417
references.citation: Aging Cell. 2006 Feb;5(1):39-50
references.pmid: 16441842
references.citation: Am J Physiol Endocrinol Metab. 2001 Oct;281(4):E757-65
references.pmid: 11551852
references.citation: Age (Dordr). 2008 Sep;30(2-3):157-68
references.pmid: 19424865
references.citation: Endocrinology. 1980 Oct;107(4):902-7
references.pmid: 7408776
references.citation: Ageing Res Rev. 2006 Feb;5(1):33-51
references.pmid: 16126012
references.citation: Genes Dev. 2003 Jun 1;17(11):1366-79
references.pmid: 12782655
references.citation: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4159-64
references.pmid: 8633033
references.citation: Science. 2009 Jul 10;325(5937):201-4
references.pmid: 19590001
references.citation: Mech Ageing Dev. 2000 Jan 10;112(3):185-96
references.pmid: 10687924
references.citation: Genes Dev. 2003 Feb 1;17(3):313-21
references.pmid: 12569120
references.citation: Eur J Clin Nutr. 2000 Jun;54 Suppl 3:S15-20
references.pmid: 11041070
references.citation: J Nutr. 2001 Mar;131(3):820-7
references.pmid: 11238765
references.citation: Endocrinology. 2000 Nov;141(11):4226-38
references.pmid: 11089557
references.citation: N Engl J Med. 1997 Oct 2;337(14):986-94
references.pmid: 9309105
references.citation: J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7
references.pmid: 12414864
references.citation: Int J Biochem Cell Biol. 2002 Nov;34(11):1340-54
references.pmid: 12200030
references.citation: Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46
references.pmid: 12543259
references.citation: Nutrition. 1989 May-Jun;5(3):155-71; discussion 172
references.pmid: 2520283
references.citation: Thyroid. 2004 Oct;14(10):825-9
references.pmid: 15588378
references.citation: Neurobiol Aging. 2008 Sep;29(9):1412-22
references.pmid: 17420071
references.citation: J Am Geriatr Soc. 1999 Jul;47(7):896-903
references.pmid: 10404938
references.citation: Endocrinology. 2005 Sep;146(9):3713-7
references.pmid: 15919745
references.citation: Ann N Y Acad Sci. 2004 Jun;1019:443-7
references.pmid: 15247063
references.citation: Neurobiol Aging. 2010 Apr;31(4):696-705
references.pmid: 18614257
references.citation: Ann N Y Acad Sci. 2004 Jun;1019:xv-xvi; 1-592
references.pmid: 15320311
references.citation: Age (Omaha). 1997 Jan;20(1):45-56
references.pmid: 23604290
references.citation: Endocrinology. 1973 Jul;93(1):156-61
references.pmid: 4197194
references.citation: Mol Endocrinol. 2006 May;20(5):1164-76
references.pmid: 16439464
references.citation: J Gerontol. 1990 Sep;45(5):B148-63
references.pmid: 2394908
references.citation: JAMA. 2006 Apr 5;295(13):1539-48
references.pmid: 16595757
references.citation: Neurobiol Aging. 2005 Jul;26(7):1117-27
references.pmid: 15748792
references.citation: Mech Ageing Dev. 2005 Sep;126(9):967-75
references.pmid: 15935442
references.citation: J Neurosci Res. 2001 Dec 15;66(6):1133-9
references.pmid: 11746446
references.citation: Am J Clin Nutr. 2003 Sep;78(3):361-9
references.pmid: 12936916
references.citation: J Appl Physiol (1985). 2003 Oct;95(4):1706-16
references.pmid: 12970376
references.citation: Science. 2002 Aug 2;297(5582):811
references.pmid: 12161648