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Abstract / Description of output
The hypothalamo-pituitary-adrenal (HPA) axis plays a critical role in regulating responses to stress and long term dysregulation of the HPA axis is associated with higher rates of mood disorders. There are circumstances where the HPA axis is more or less responsive to stress. For example, during late pregnancy ACTH and corticosterone responses to stress are markedly suppressed, whereas in offspring born to mothers that experienced repeated stress during pregnancy, the HPA axis is hyper-responsive to stress.
Neuroactive steroids such as allopregnanolone, tetrahydrodeoxycorticosterone (THDOC) and androstanediol can modulate HPA axis activity and concentrations of some neuroactive steroids in the brain are altered during pregnancy and following stress. Thus, here altered neurosteroidogenesis is proposed as a mechanism that could underpin the dynamic changes in HPA axis regulation typically observed in late pregnant and in prenatally stressed individuals. In support of this hypothesis, evidence in rats demonstrates that elevated levels of allopregnanolone in pregnancy induce a central inhibitory opioid mechanism that serves to minimize stress-induced HPA axis activity. Conversely, in prenatally stressed rodents, where HPA axis stress responses are enhanced, evidence indicates the capacity of the brain for neurosteroidogenesis is reduced.
Understanding the mechanisms involved in adaptations in HPA axis regulation may provide insights for manipulating stress sensitivity and for developing therapies for stress-related disorders in humans.
Neuroactive steroids such as allopregnanolone, tetrahydrodeoxycorticosterone (THDOC) and androstanediol can modulate HPA axis activity and concentrations of some neuroactive steroids in the brain are altered during pregnancy and following stress. Thus, here altered neurosteroidogenesis is proposed as a mechanism that could underpin the dynamic changes in HPA axis regulation typically observed in late pregnant and in prenatally stressed individuals. In support of this hypothesis, evidence in rats demonstrates that elevated levels of allopregnanolone in pregnancy induce a central inhibitory opioid mechanism that serves to minimize stress-induced HPA axis activity. Conversely, in prenatally stressed rodents, where HPA axis stress responses are enhanced, evidence indicates the capacity of the brain for neurosteroidogenesis is reduced.
Understanding the mechanisms involved in adaptations in HPA axis regulation may provide insights for manipulating stress sensitivity and for developing therapies for stress-related disorders in humans.
Original language | English |
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Pages (from-to) | 160-168 |
Journal | Journal of Steroid Biochemistry and Molecular Biology |
Volume | 160 |
Early online date | 17 Aug 2015 |
DOIs | |
Publication status | Published - Jun 2016 |
Event | 8th International Meeting Steroids and Nervous System - Torino, Italy Duration: 14 Feb 2015 → 18 Feb 2015 |
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Dive into the research topics of 'Neuroactive steroids and stress axis regulation: pregnancy and beyond'. Together they form a unique fingerprint.Activities
- 1 Invited talk
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Sex-specific programming of the brain and behaviour by prenatal stress
Paula Brunton (Invited speaker)
2 Jun 2017Activity: Academic talk or presentation types › Invited talk