Sex Differences in Acute Neuroendocrine Responses to Stressors in Rodents and Humans
- 6 June 2022
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Cold Spring Harbor Perspectives in Biology
- Vol. 14 (9), a039081
- https://doi.org/10.1101/cshperspect.a039081
Abstract
Sex differences in the neuroendocrine response to acute stress occur in both animals and humans. In rodents, stressors such as restraint and novelty induce a greater activation of the hypothalamic-pituitary-adrenal axis (HPA) in females compared to males. The nature of this difference arises from steroid actions during development (organizational effects) and adulthood (activational effects). Androgens decrease HPA stress responsivity to acute stress, while estradiol increases it. Androgenic down-regulation of HPA responsiveness is mediated by the binding of testosterone (T) and dihydrotestosterone (DHT) to the androgen receptor, as well as the binding of the DHT metabolite, 3β-diol, to the β form of the estrogen receptor (ERβ). Estradiol binding to the α form of the estrogen receptor (ERα) increases HPA responsivity. Studies of human sex differences are relatively few and generally employ a psychosocial paradigm to measure stress-related HPA activation. Men consistently show greater HPA reactivity than women when being evaluated for achievement. Some studies have found greater reactivity in women when being evaluated for social performance. The pattern is inconsistent with rodent studies but may involve the differential nature of the stressors employed. Psychosocial stress is nonphysical and invokes a significant degree of top-down processing that is not easily comparable to the types of stressors employed in rodents. Gender identity may also be a factor based on recent work showing that it influences the neural processing of positive and negative emotional stimuli independent of genetic sex. Comparing different types of stressors and how they interact with gender identity and genetic sex will provide a better understanding of sex steroid influences on stress-related HPA reactivity.Keywords
This publication has 112 references indexed in Scilit:
- Male rats with the testicular feminization mutation of the androgen receptor display elevated anxiety-related behavior and corticosterone response to mild stressHormones and Behavior, 2011
- Androgen Receptors in the Posterior Bed Nucleus of the Stria Terminalis Increase Neuropeptide Expression and the Stress-Induced Activation of the Paraventricular Nucleus of the HypothalamusNeuropsychopharmacology, 2011
- The Role of Oestradiol in Sexually Dimorphic Hypothalamic‐Pituitary‐Adrena Axis Responses to Intracerebroventricular Ethanol Administration in the RatJournal of Neuroendocrinology, 2009
- Defining brain region-specific glucocorticoid action during stress by conditional gene disruption in miceBrain Research, 2009
- Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memoryProceedings of the National Academy of Sciences of the United States of America, 2009
- A Role for the Androgen Metabolite, 5α‐Androstane‐3β,17β‐Diol, in Modulating Oestrogen Receptor β‐Mediated Regulation of Hormonal Stress ReactivityJournal of Neuroendocrinology, 2009
- Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic–pituitary–adrenal axis via estrogen receptor alpha within the hypothalamusNeuroscience, 2009
- Psychological Stress and DiseaseJAMA, 2007
- Sex differences in ACTH pulsatility following metyrapone blockade in patients with major depressionPsychoneuroendocrinology, 2007
- Gender difference in neural response to psychological stressSocial Cognitive and Affective Neuroscience, 2007