Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone
Allopregnanolone and pregnanolone—neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis—have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major depression, post-partum depression, pre-menstr...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-12-01
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| Series: | Chronic Stress |
| Online Access: | https://doi.org/10.1177/2470547018818555 |
| _version_ | 1818283332387995648 |
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| author | Jennifer J. Liang Ann M. Rasmusson |
| author_facet | Jennifer J. Liang Ann M. Rasmusson |
| author_sort | Jennifer J. Liang |
| collection | DOAJ |
| description | Allopregnanolone and pregnanolone—neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis—have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major depression, post-partum depression, pre-menstrual dysphoric disorder, chronic pain, Parkinson’s disease, Alzheimer’s disease, neurotrauma, and stroke. Allopregnanolone and pregnanolone equipotently facilitate the effects of gamma-amino-butyric acid (GABA) at GABA A receptors, and when sulfated, antagonize N-methyl-D-aspartate receptors. They play myriad roles in neurophysiological homeostasis and adaptation to stress while exerting anxiolytic, antidepressant, anti-nociceptive, anticonvulsant, anti-inflammatory, sleep promoting, memory stabilizing, neuroprotective, pro-myelinating, and neurogenic effects. Given that these neurosteroids are synthesized de novo on demand, this review details the molecular steps involved in the biochemical conversion of cholesterol to allopregnanolone and pregnanolone within steroidogenic cells. Although much is known about the early steps in neurosteroidogenesis, less is known about transcriptional, translational, and post-translational processes in allopregnanolone- and pregnanolone-specific synthesis. Further research to elucidate these mechanisms as well as to optimize the timing and dose of interventions aimed at altering the synthesis or levels of these neurosteroids is much needed. This should include the development of novel therapeutics for the many neuropsychiatric conditions to which dysregulation of these neurosteroids contributes. |
| first_indexed | 2024-12-13T00:35:14Z |
| format | Article |
| id | doaj.art-204406944b314e79b92a37152ebfd7a4 |
| institution | Directory Open Access Journal |
| issn | 2470-5470 |
| language | English |
| last_indexed | 2024-12-13T00:35:14Z |
| publishDate | 2018-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Chronic Stress |
| spelling | doaj.art-204406944b314e79b92a37152ebfd7a42022-12-22T00:05:13ZengSAGE PublishingChronic Stress2470-54702018-12-01210.1177/2470547018818555Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and PregnanoloneJennifer J. Liang0Ann M. Rasmusson1Boston University School of Medicine, Boston, MA, USAVA Boston Healthcare System, Boston, MA, USAAllopregnanolone and pregnanolone—neurosteroids synthesized from progesterone in the brain, adrenal gland, ovary and testis—have been implicated in a range of neuropsychiatric conditions including seizure disorders, post-traumatic stress disorder, major depression, post-partum depression, pre-menstrual dysphoric disorder, chronic pain, Parkinson’s disease, Alzheimer’s disease, neurotrauma, and stroke. Allopregnanolone and pregnanolone equipotently facilitate the effects of gamma-amino-butyric acid (GABA) at GABA A receptors, and when sulfated, antagonize N-methyl-D-aspartate receptors. They play myriad roles in neurophysiological homeostasis and adaptation to stress while exerting anxiolytic, antidepressant, anti-nociceptive, anticonvulsant, anti-inflammatory, sleep promoting, memory stabilizing, neuroprotective, pro-myelinating, and neurogenic effects. Given that these neurosteroids are synthesized de novo on demand, this review details the molecular steps involved in the biochemical conversion of cholesterol to allopregnanolone and pregnanolone within steroidogenic cells. Although much is known about the early steps in neurosteroidogenesis, less is known about transcriptional, translational, and post-translational processes in allopregnanolone- and pregnanolone-specific synthesis. Further research to elucidate these mechanisms as well as to optimize the timing and dose of interventions aimed at altering the synthesis or levels of these neurosteroids is much needed. This should include the development of novel therapeutics for the many neuropsychiatric conditions to which dysregulation of these neurosteroids contributes.https://doi.org/10.1177/2470547018818555 |
| spellingShingle | Jennifer J. Liang Ann M. Rasmusson Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone Chronic Stress |
| title | Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone |
| title_full | Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone |
| title_fullStr | Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone |
| title_full_unstemmed | Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone |
| title_short | Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone |
| title_sort | overview of the molecular steps in steroidogenesis of the gabaergic neurosteroids allopregnanolone and pregnanolone |
| url | https://doi.org/10.1177/2470547018818555 |
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