Cited by 130Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchPosttraumatic Stress Disorder Research

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

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Almeida, Felipe Borges, Pinna, Graziano, Barros, Helena Maria Tannhauser·2021·International Journal of Molecular Sciences

Abstract

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

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  • Allopregnanolone induces GABAergic inhibition of HPA axis activation in female rats and pregnant women.

    “Allopregnanolone has induced the GABAergic inhibition of HPA axis activation in female rats [93,94] and pregnant women [95].”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [94]

    Section 3 describes allopregnanolone attenuating the endocrine stress response, probably through GABA-mediated inhibition of CRH neurons, and discusses effects in rats. Section 5 discusses pregnancy and postpartum depression, but does not report that allopregnanolone induces GABAergic inhibition of HPA-axis activation in pregnant women—the population specifically attached to this citation. (LLM, conf=0.84)

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Authors
Almeida, F. B., Pinna, G., & Barros, H. M. T.
Affiliations
  • Universidade Federal de Ciências da Saúde de Porto Alegre (BR)
  • University of Illinois Chicago (US)
Corresponding author
Pinna, Graziano
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-05-23
Volume
22
Issue
11
Pages
5495
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3164510424
Cited by
130
References
84
Citations by year
2026: 17 · 2025: 39 · 2024: 30 · 2023: 26 · 2022: 16 · 2021: 2
FWCI
2.23
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ((Code 001))
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (19/2551, Code 001)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Keywords
hypothalamic-pituitary-adrenal axis, allopregnanolone, major depressive disorder, post-traumatic stress disorder, neurosteroids, GABAergic modulation, chronic stress, cortisol, dexamethasone suppression test, biomarkers, treatment goals
MeSH terms
Adaptation, Physiological, Animals, Antidepressive Agents, Chronic Disease, Corticosterone, Depressive Disorder, Major, Major Depressive Disorder, Female, gamma-Aminobutyric Acid, Humans, Hypothalamo-Hypophyseal System, Male, Models, Biological, Pituitary-Adrenal System, Pregnanolone, Receptors, GABA-A, Sex Characteristics, Stress, Physiological, Stress Disorders, Post-Traumatic, Stress, Psychological, Feedback, Physiological, GABA-A Receptor Agonists

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