Impact of Moderate Calorie Restriction on the Reproductive Neuroendocrine Axis of Male Rhesus Macaques.
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.
Sitzmann
Brandon D
BD
Department of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon 97006.
Mattison
Julie A
JA
Ingram
Donald K
DK
Roth
George S
GS
Ottinger
Mary Ann
MA
Urbanski
Henryk F
HF
Aging Cell. 2004 Feb;3(1):7-12
14965349
Biostatistics. 2003 Apr;4(2):249-64
12925520
J Clin Endocrinol Metab. 2001 Feb;86(2):724-31
11158037
Toxicol Sci. 1999 Dec;52(2 Suppl):41-8
10630589
Endocrinology. 1998 May;139(5):2284-6
9564835
J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):B98-107
11253152
Brain Res. 1997 Jan 2;744(1):96-104
9030417
Aging Cell. 2006 Feb;5(1):39-50
16441842
Am J Physiol Endocrinol Metab. 2001 Oct;281(4):E757-65
11551852
Age (Dordr). 2008 Sep;30(2-3):157-68
19424865
Endocrinology. 1980 Oct;107(4):902-7
7408776
Ageing Res Rev. 2006 Feb;5(1):33-51
16126012
Genes Dev. 2003 Jun 1;17(11):1366-79
12782655
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4159-64
8633033
Science. 2009 Jul 10;325(5937):201-4
19590001
Mech Ageing Dev. 2000 Jan 10;112(3):185-96
10687924
Genes Dev. 2003 Feb 1;17(3):313-21
12569120
Eur J Clin Nutr. 2000 Jun;54 Suppl 3:S15-20
11041070
J Nutr. 2001 Mar;131(3):820-7
11238765
Endocrinology. 2000 Nov;141(11):4226-38
11089557
N Engl J Med. 1997 Oct 2;337(14):986-94
9309105
J Clin Endocrinol Metab. 2002 Nov;87(11):5001-7
12414864
Int J Biochem Cell Biol. 2002 Nov;34(11):1340-54
12200030
Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46
12543259
Nutrition. 1989 May-Jun;5(3):155-71; discussion 172
2520283
Thyroid. 2004 Oct;14(10):825-9
15588378
Neurobiol Aging. 2008 Sep;29(9):1412-22
17420071
J Am Geriatr Soc. 1999 Jul;47(7):896-903
10404938
Endocrinology. 2005 Sep;146(9):3713-7
15919745
Ann N Y Acad Sci. 2004 Jun;1019:443-7
15247063
Neurobiol Aging. 2010 Apr;31(4):696-705
18614257
Ann N Y Acad Sci. 2004 Jun;1019:xv-xvi; 1-592
15320311
Age (Omaha). 1997 Jan;20(1):45-56
23604290
Endocrinology. 1973 Jul;93(1):156-61
4197194
Mol Endocrinol. 2006 May;20(5):1164-76
16439464
J Gerontol. 1990 Sep;45(5):B148-63
2394908
JAMA. 2006 Apr 5;295(13):1539-48
16595757
Neurobiol Aging. 2005 Jul;26(7):1117-27
15748792
Mech Ageing Dev. 2005 Sep;126(9):967-75
15935442
J Neurosci Res. 2001 Dec 15;66(6):1133-9
11746446
Am J Clin Nutr. 2003 Sep;78(3):361-9
12936916
J Appl Physiol (1985). 2003 Oct;95(4):1706-16
12970376
Science. 2002 Aug 2;297(5582):811
12161648