TY - JOUR
T1 - Neuroendocrine stress response is moderated by sex and sex hormone receptor polymorphisms
AU - Hastings, W. J.
AU - Chang, A. M.
AU - Ebstein, R. P.
AU - Shalev, I.
N1 - Funding Information:
Original data collection was supported by the Israel Science Foundation (Grant No. 389/05) and partially by Phillip Morris USA & Phillip Morris International (RPE). Secondary data analysis was supported by University Distinguished Graduate Fellowship (Penn State University).
Publisher Copyright:
© 2018
PY - 2018/11
Y1 - 2018/11
N2 - Sex hormones are significant regulators of stress reactivity, however, little is known about how genetic variation in hormone receptors contributes to this process. Here we report interactions between biological sex and repeat polymorphisms in genes encoding sex hormone receptors, and their effects on salivary cortisol reactivity in a sample of 100 participants (47 men & 53 women; 24.7 ± 3.23 years). Three genes were investigated: estrogen receptors alpha (ESR1) and beta (ESR2), and the androgen receptor (AR). Participants were classified as carrying 'short’ or ‘Long’ alleles based on median splits of the repeat distribution for each gene. Measures of physiological reactivity were collected before and after exposure to a canonical laboratory stressor and converted to traditional summary measures for analyses. Overall, men exhibited greater cortisol (p = 0.001) and mean arterial pressure reactivity (p = 0.002), while women displayed elevated heart rate throughout the session (p = 0.02). The effect of polymorphisms on salivary cortisol was sex sensitive. ESR1 was associated with differential reactivity in men (p = 0.04), but not women (p = 0.24). ESR2 genotype interacted with sex such that each additional ‘Long’ allele was associated with a 6.4% decrease in salivary cortisol in men, but a 9.5% increase in the levels of women (p = 0.02 for interaction). For the X-linked AR, the ‘Long’ allele was associated with decreased cortisol levels in men (p = 0.047), but in women had no effect (p = 0.75). Together, these results provide evidence for the saliency of genetic variation in sex hormone receptors on stress reactivity in humans and highlight their important role as mediators of hormonal activity.
AB - Sex hormones are significant regulators of stress reactivity, however, little is known about how genetic variation in hormone receptors contributes to this process. Here we report interactions between biological sex and repeat polymorphisms in genes encoding sex hormone receptors, and their effects on salivary cortisol reactivity in a sample of 100 participants (47 men & 53 women; 24.7 ± 3.23 years). Three genes were investigated: estrogen receptors alpha (ESR1) and beta (ESR2), and the androgen receptor (AR). Participants were classified as carrying 'short’ or ‘Long’ alleles based on median splits of the repeat distribution for each gene. Measures of physiological reactivity were collected before and after exposure to a canonical laboratory stressor and converted to traditional summary measures for analyses. Overall, men exhibited greater cortisol (p = 0.001) and mean arterial pressure reactivity (p = 0.002), while women displayed elevated heart rate throughout the session (p = 0.02). The effect of polymorphisms on salivary cortisol was sex sensitive. ESR1 was associated with differential reactivity in men (p = 0.04), but not women (p = 0.24). ESR2 genotype interacted with sex such that each additional ‘Long’ allele was associated with a 6.4% decrease in salivary cortisol in men, but a 9.5% increase in the levels of women (p = 0.02 for interaction). For the X-linked AR, the ‘Long’ allele was associated with decreased cortisol levels in men (p = 0.047), but in women had no effect (p = 0.75). Together, these results provide evidence for the saliency of genetic variation in sex hormone receptors on stress reactivity in humans and highlight their important role as mediators of hormonal activity.
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U2 - 10.1016/j.yhbeh.2018.10.002
DO - 10.1016/j.yhbeh.2018.10.002
M3 - Article
C2 - 30300610
AN - SCOPUS:85054559418
SN - 0018-506X
VL - 106
SP - 74
EP - 80
JO - Hormones and Behavior
JF - Hormones and Behavior
ER -