Neuroactive steroids and stress axis regulation: pregnancy and beyond

Research output: Contribution to journalReview articlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)160-168
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume160
Early online date17 Aug 2015
DOIs
Publication statusPublished - Jun 2016
Event8th International Meeting Steroids and Nervous System - Torino, Italy
Duration: 14 Feb 201518 Feb 2015

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