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Apart from exerting effects on the genome via intracellular steroid receptors, 'neuroactive steroids' (or 'neurosteroids') rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. Several of these steroids accumulate in the brain after local synthesis or after metabolism of adrenal steroids. The 3alpha-hydroxy ring A-reduced pregnane steroids allopregnanolone and tetrahydrodeoxycorticosterone have been surmised to enhance GABA-mediated chloride currents, whereas pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate display functional antagonistic properties at GABA A receptors.
Neurosteroids are synthesized in the central and peripheral nervous system, especially in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. They include 3 beta-hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha,5 alpha-THPROG). These compounds can act as allosteric modulators of neurotransmitter receptors, such as GABA(A), NMDA, and sigma receptors. Progesterone (PROG) is also a neurosteroid, and a progesterone receptor (PROG-R) has been identified in peripheral and central glial cells.
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References

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References

1. Neurosteroid modulation of synaptic and extrasynaptic GABA_A receptors, Herd MB, Belelli D, Lambert JJ, , , , 2007
2. Endogenous neurosteroids regulate GABA_A receptors through two discrete transmembrane sites, Hosie AM, Wilkins ME, da Silva HM, Smart TG, , , Nature, 2006
3. Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis, Agís-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A, , , Proc. Natl. Acad. Sci. U.S.A., 2006
4. Neurosteroid access to the GABA_A receptor, Akk G, Shu HJ, Wang C, Steinbach JH, Zorumski CF, Covey DF, Mennerick S, , , J. Neurosci., 2005
5. Neurosteroids: endogenous regulators of the GABA_A receptor, Belelli D, Lambert JJ, , , Nat. Rev. Neurosci., 2005
6. Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake, Pinna G, Costa E, Guidotti A, , , Psychopharmacology (Berl.), 2006
7. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression, Wang JM, Johnston PB, Ball BG, Brinton RD, , , J. Neurosci., 2005
8. Steroids, neuroactive steroids and neurosteroids in psychopathology, Dubrovsky BO, , , Prog. Neuropsychopharmacol. Biol. Psychiatry, 2005
9. Neurosteroids: biochemistry and clinical significance, Mellon SH, Griffin LD, , , Trends Endocrinol. Metab., 2002
10. Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation, Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A, , , Proc. Natl. Acad. Sci. U.S.A., 2001
11. Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation, Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A, , , Proc. Natl. Acad. Sci. U.S.A., 2001
12. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine, Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A, , , Proc. Natl. Acad. Sci. U.S.A., 1998
13. Progesterone 5-alpha-reduction in neuronal and in different types of glial cell cultures: type 1 and 2 astrocytes and oligodendrocytes, Melcangi RC, Celotti F, Martini L, , , Brain Res., 1994
14. Progesterone receptor-mediated effects of neuroactive steroids, Rupprecht R, Reul JM, Trapp T, van Steensel B, Wetzel C, Damm K, Zieglgänsberger W, Holsboer F, , , Neuron, 1993
15. Neurosteroids act on recombinant human GABA_A receptors, Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E, , , Neuron, 1990
16. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor, Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM, , , Science, 1986
17. Characterization and measurement of dehydroepiandrosterone sulfate in rat brain, Corpéchot C, Robel P, Axelson M, Sjövall J, Baulieu EE, , , Proc. Natl. Acad. Sci. U.S.A., 1981

See also

★ 5-alpha reductase

★ GABA A receptor

★ List of neurosteroids

External links

★ A clinical research study

★ Neurosteroids: of the nervous system, by the nervous system, for the nervous system
pl.Neurosteroidy