2019
DOI: 10.1111/ejn.14615
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Abstract: The hypothalamo-pituitary-adrenal (HPA) axis plays a key role in the neuroendocrine response to stress and in maintaining physiological homeostasis. However, stress that is chronic in nature can lead to HPA axis dysfunction and increase the risk for developing affective disorders, particularly if the stress is experienced during vulnerable periods in life. Sex differences in how the HPA axis responds to stress are well established, with females typically displaying heightened responses. The underlying cause of… Show more

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Cited by 48 publications
(27 citation statements)
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References 322 publications
(304 reference statements)
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“…Moreover, the central expression of key enzymes involved in neuroactive steroid synthesis is sexually dimorphic, 59 which may contribute to sex differences in neuroactive steroid levels in the brain. The impact of these sex differences on function are unclear; however, given the well established roles of neuroactive steroids in modulating stress responses and mood, 16,26,27 differences in neuroactive steroid concentrations in the brain between males and female may contribute to the sex differences in HPA axis regulation and susceptibility to psychiatric disorders 29,60‐62 …”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Moreover, the central expression of key enzymes involved in neuroactive steroid synthesis is sexually dimorphic, 59 which may contribute to sex differences in neuroactive steroid levels in the brain. The impact of these sex differences on function are unclear; however, given the well established roles of neuroactive steroids in modulating stress responses and mood, 16,26,27 differences in neuroactive steroid concentrations in the brain between males and female may contribute to the sex differences in HPA axis regulation and susceptibility to psychiatric disorders 29,60‐62 …”
Section: Discussionmentioning
confidence: 99%
“…Therefore, the present study aimed to compare the neuroactive steroid milieu of control and PNS offspring under basal conditions, as well as following exposure to an acute stressor. Specifically, we quantified nine neuroactive steroids (Figure 1) that are known mediators of the stress response, including corticosterone, the end product of HPA axis activation; the positive GABA A receptor modulators, allopregnanolone and THDOC; their precursors, dihydroprogesterone (DHP) and progesterone, as well as dihydrodeoxycorticosterone (DHDOC) and DOC, respectively; and lastly testosterone, which contributes to sex differences in the stress response 29 . These steroids were measured in five distinct brain regions: the hypothalamus, where stress‐related circuitry are integrated; the hippocampus, amygdala and the prefrontal cortex, which are limbic areas that together process stressful experiences; and the brainstem, an area that receives inputs regarding homeostatic perturbations 30 .…”
Section: Introductionmentioning
confidence: 99%
“…The synthesis of neurosteroids occurs in nerve cells in various brain regions, including glutamatergic pyramidal neurons in the cortex, hippocampus, and the basolateral amygdala [ 60 , 61 ]. Previous studies on rats and mice indicated that acute stressors such as swim stress, CO 2 inhalation, and LPS treatment were associated with increases in neuroactive steroid concentrations in the plasma and brain [ 14 , 62 , 63 , 64 ]. Purdy et al [ 14 ] showed that the AL concentration in the rat brain (cerebral cortex and hypothalamus) increased for an hour after stress initiation, prior to peaking in the plasma.…”
Section: Discussionmentioning
confidence: 99%
“…In this aspect, AL was shown to enhance GABA-mediated inhibitory action on PVN neurons by interacting with the membrane-bound GABA A receptors [ 66 ]. A protective action of AL against stress hormones, as well as its other beneficial effects on the CNS, have been widely documented in rodents and humans [ 64 ]. The presented research demonstrated that the protective effect of AL could also involve a DNA defense mechanism.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, corticosterone effects in the brain may result in sex-differentiated F I G U R E 1 Following adult adrenalectomy and stable corticosterone replacement (ADXR) the male behavior (immobility duration) in the second session of the forced swim test was affected in ADXR male rats, in comparison to sham-operated males, whereas the female behavioral response remained unaffected. Adapted from Kokras Another factor contributing to this intricate relationship between serum corticosterone and behavioral outcomes in females may be the interplay between the HPA axis and the hypothalamic-pituitary-gonadal axis, and estrogens, in particular (Sze & Brunton, 2019). Although a detailed presentation of the subject is beyond the scope of this review, it would be prudent to briefly mention some interactions.…”
Section: Con Clus Ionmentioning
confidence: 99%