Neurosteroids: biochemistry and clinical significance

@article{Mellon2002NeurosteroidsBA,
  title={Neurosteroids: biochemistry and clinical significance},
  author={Synthia H Mellon and Lisa D Griffin},
  journal={Trends in Endocrinology \& Metabolism},
  year={2002},
  volume={13},
  pages={35-43}
}
The brain, like the adrenals, gonads and the placenta, is a steroidogenic tissue. However, unlike classic steroidogenic tissues, the synthesis of steroids in the nervous system requires coordinated expression and regulation of genes encoding the steroidogenic enzymes in several different cell types (neurons and glia) at different locations in the nervous system, often at some distance from the cell bodies. Furthermore, the synthesis of these steroids might be developmentally regulated and… 
View on Elsevier
doi.org
469 Citations
Highly Influential Citations
21
Background Citations
147
Methods Citations
5

469 Citations

Citation Type

Citation Type

The relevance of neurosteroids to clinical psychiatry: From the laboratory to the bedside
TLDR
It has been suggested that neurosteroids may become potential targets for pharmacological intervention in the future with further neurosteroid investigation contributing to a more comprehensive understanding of human behavior and psychopathology.
Neurosteroid biosynthesis: Enzymatic pathways and neuroendocrine regulation by neurotransmitters and neuropeptides
TLDR
The observation that the activity of key steroidogenic enzymes is finely tuned by various neurotransmitters and neuropeptides strongly suggests that some of the central effects of these neuromodulators may be mediated via the regulation of neurosteroid production.
Neurosteroids: Endogenous modulators of neuronal excitability and plasticity
TLDR
Steroidogenesis in the nervous system is regulated by interactions between neurons and glial cells, and drugs that affect synthesis or metabolism of neurosteroids provide a new therapeutic opportunity for treatment of these disorders.
Regulation of Neurosteroid Biosynthesis by Neurotransmitters and Neuropeptides
TLDR
It has been found that glutamate, acting through kainate and/or AMPA receptors, rapidly inactivates P450arom, and that melatonin production by the pineal gland and eye inhibits the biosynthesis of 7α-hydroxypregnenolone, while prolactin produced by the adenohypophysis enhances the formation of 7 α-OH-Δ5P.
Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant
  • R. Guennoun
  • Biology, Medicine
    International journal of molecular sciences
  • 2020
TLDR
The biosynthetic pathways and the expression of enzymes and receptors of progesterone; as well as the changes observed after brain injuries and in neurological diseases; and the key role of the classical progester one receptors (PR) in mediating the neuroprotective effects of progestersone after stroke are highlighted.
Neurosteroidogenic enzymes: CYP11A1 in the central nervous system
TLDR
The discrepancies in the current evidence for CYP11A1 in the central nervous system are highlighted and new directions for understanding neurosteroidogenesis are proposed, which will be crucial for developing neurosteroids-based therapies for the future.
Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors.
TLDR
Given the ubiquitous expression of the GABA(A) receptor throughout the mammalian central nervous system (CNS), physiological, pathophysiological, or drug-induced pertubations of neurosteroid levels may be expected to produce widespread changes in brain excitability, however, the neurosteroids/GABA(A), receptor interaction is brain region and indeed neuron specific.
Neurosteroid Metabolites of Gonadal Steroid Hormones in Neuroprotection: Implications for Sex Differences in Neurodegenerative Disease
TLDR
The hypothesis that differences between males and females in local neurosteroid production may contribute to sex differences in the development of neurodegenerative disease is explored.
Steroid Biosynthesis within the Frog Brain
TLDR
Data indicate that some of the neurophysiological effects of neurotransmitters and neuropeptides may be mediated through modulation of neurosteroid biosynthesis.
Revisiting the roles of progesterone and allopregnanolone in the nervous system: Resurgence of the progesterone receptors
TLDR
Effects of progesterone on the nervous system via PR, and of allopregnanolone via its modulation of GABA(A) receptors, are critically discussed, with main focus on the brain.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 92 REFERENCES
Neurosteroids: Biosynthesis and Function of These Novel Neuromodulators
TLDR
This paper summarizes what is known about the biosynthesis of neurosteroids, the enzymes mediating these reactions, their localization during development and in the adult, and their function and mechanisms of action in the developing and adult central and peripheral nervous systems.
NEUROSTEROIDS: A NOVEL FUNCTION OF THE BRAIN
  • E. Baulieu
  • Medicine, Biology
    Psychoneuroendocrinology
  • 1998
TLDR
A physiological function of neurosteroids in the central nervous system is strongly suggested by the role of hippocampal PREGS with respect to memory, observed in aging rats and it may be important to study the effect of abnormal neurosteroid concentrations/metabolism with a view to the possible treatment of functional and trophic disturbances of the nervous system.
Expression of the steroidogenic enzyme P450scc in the central and peripheral nervous systems during rodent embryogenesis.
TLDR
It is demonstrated that P450scc is expressed in the nervous system of the developing rodent embryo in cell lineages derived from the neural crest and the sites of expression are located mainly in sensory structures of the peripheral nervous system during embryogenesis, suggesting a possible function in coordinating environmental cues and behavior and in the development and organization of the nervous System.
Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system.
TLDR
It is demonstrated that P450c17 is expressed in the nervous system of the developing rodent embryo, suggesting it is a marker for the axonal growth in this region, and that its neurosteroid product may be a signal for targeting cortical axons during embryogenesis.
Neurosteroids : a new regulatory function in the nervous system
Neurosteroids: From Definition and Biochemistry to Physiopathologic Function, Paul Robel, Michael Schumacher, and Etienne-Emile Baulieu. Molecular Biology and Developmental Regulation of the Enzymes…
Neuropsychopharmacological properties of neuroactive steroids
TLDR
It is demonstrated that the 3alpha-hydroxy ring A-reduced neuroactive steroids can regulate also gene expression via the progesterone receptor after intracellular oxidation and provide a new role for the therapeutic application of these steroids in neurology and psychiatry.
Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system.
TLDR
Steroid hormones, which are synthesized in the adrenal gland, gonads and placenta, exert a large array of biological effects on the nervous system, including development, growth, maturation, and differentiation of the central nervous system.
Neurosteroids and GABAA receptor function.
TLDR
Recent advances in this field are reviewed and the therapeutic potential of this novel, non-genomic effect of steroids is discussed and whether they may influence behaviour under physiological, or pathophysiological, conditions is investigated.
Neurosteroid biosynthesis: genes for adrenal steroidogenic enzymes are expressed in the brain
TLDR
Some of the same enzymes involved in steroidogenesis in classic endocrine tissues are found in a cell-specific and region-specific fashion in the brain.
Modulation of steroidal levels by adrenalectomy/castration and inhibition of neurosteroid synthesis enzymes affect σ1 receptor‐mediated behaviour in mice
TLDR
Investigation of the effects of inhibitors of key enzymes involved in neurosteroid synthesis in adrenalectomized/castrated mice revealed that, among neurosteroids, progesterone may be the main modulator of σ1 receptors.
...
1
2
3
4
5
...