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Neuroendocrine stress response is moderated by sex and sex hormone receptor polymorphisms.

ABSTRACT: 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.

SUBMITTER: Hastings WJ

PROVIDER: S-EPMC6324727 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Neuroendocrine stress response is moderated by sex and sex hormone receptor polymorphisms.

Hastings W J WJ Chang A M AM Ebstein R P RP Shalev I I

Hormones and behavior 20181011

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 ...[more]

PMID: 30300610

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Project description:Pituitary GH-secretory profiles are sex dependent and regulate the sexually dimorphic expression of a large number of genes in the liver. The slow response of many sex-specific liver genes to changes in plasma GH status suggests that GH acts in the liver via both direct and indirect mechanisms organized in a hierarchical regulatory network. Presently, genome-wide liver transcription profiling was conducted to elucidate the global impact of pituitary hormone ablation on the sex specificity of rat liver gene expression and to identify sex-specific genes that respond rapidly to GH as candidates for direct targets of GH action. Hypophysectomy abolished the sex specificity of approximately 90% of 1032 sex-dependent genes, consistent with the dominant role of pituitary GH in regulating liver sexual dimorphism. Two major classes of sex-specific genes were identified: genes that were down-regulated after hypophysectomy and may be subject to positive GH regulation (461 class I genes), and genes that were up-regulated after hypophysectomy and may be subject to negative GH regulation (224 class II genes). Fifty class I sex-specific genes were induced, and 38 class II sex-specific genes were suppressed within 90 min of a physiological GH pulse, suggesting they are primary GH response genes. A further 71 sex-specific genes responded after a second GH treatment and may correspond to secondary response genes. Twenty four DNA-binding proteins were identified as early GH response genes, of which 15 were induced and nine were suppressed by GH. Five of these 24 genes displayed sex-specific expression, consistent with a hierarchical transcriptional network controlling sex-specific liver gene expression. Class II male-specific genes, such as Cyp2a2 and Cyp2c13, were down-regulated within 30 min of GH pulse treatment, as determined by heterogeneous nuclear RNA analysis, suggesting that transcription of these genes is restricted to the GH-free interpulse period in adult male rat liver. We conclude that GH acts via both positive and negative regulatory mechanisms to establish and maintain the sex specificity of liver gene expression.

Dataset Information

Neuroendocrine stress response is moderated by sex and sex hormone receptor polymorphisms.

Publications

Neuroendocrine stress response is moderated by sex and sex hormone receptor polymorphisms.

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