Abstract # 163:

Scheduled for Friday, August 19, 2005 07:00 PM-09:00 PM: (Cambridge/Oxford Room) Poster Presentation


A POLYMORPHISM IN THE CORTICOTROPIN-RELEASING HORMONE GENE PROMOTER IS ASSOCIATED WITH INCREASED HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVITY FOLLOWING STRESS IN RHESUS MACAQUES (Macaca mulatta)

M. Gupte1, C. S. Barr1,2, R. L. Dvoskin1,2, T. K. Newman1,2, S. Higley3, D. Goldman1, S. J. Suomi3 and J. D. Higley2
1LNG/NIAAA/NIH, 5625 Fishers Ln, Room3S32, Rockville, MD 20852, 2LCTS/NIAAA/NIH, NIH Animal Center, PO Box 529, Poolesville, MD, 20837 , 3LCE/NICHD/NIH
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     Corticotropin-releasing hormone (CRH) is the primary neuropeptide responsible for hypothalamic-pituitary-adrenal (HPA) axis activation. The CRH gene is a good candidate for investigating genetic variation as it relates to vulnerability to stress. We have identified a number of polymorphisms within the 5’flanking region for the rhesus CRH gene. One of these polymorphisms (-248C>T) is present within a highly-conserved region known to be critical to regulation of CRH transcription. We wanted to determine whether the CRH –248 C>T variant would influence stress axis activity during baseline conditions and in response to social separation stress in infant macaques. At 6 months of age, animals (N=232) were subjected to social separation. Adrenocorticotropin (ACTH) and cortisol levels were determined at baseline and following 1, 2 and 96h of separation. The influence of CRH gene promoter variation on HPA response was analyzed using repeated measures ANOVA. Both ACTH and cortisol increased in response to social separation. There were interactive effects of the –248 C>T polymorphism with social separation on serum levels of ACTH (P = 0.001) and cortisol (P = 0.006). The –248 T allele was associated with both increased ACTH (P = 0.03) and cortisol responses (P = 0.04), but only following stress. These data demonstrate that CRH gene promoter variation influences HPA axis activity in rhesus macaques and suggest a potential role for CRH gene variation in the vulnerability to stress.