Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor

Maria Dorota Majewska, Neil L. Harrison, Rochelle D. Schwartz, Jeffery L. Barker, Steven M. Paul

Research output: Contribution to journalArticle

1910 Scopus citations

Abstract

Two metabolites of the steroid hormones progesterone and deoxycorticosterone, 3α-hydroxy-5α-dihydroprogesterone and 3α,5α-tetrahydrodeoxycorticosterone, are potent barbiturate-like ligands of the γ-aminobutyric acid (GABA) receptor-chloride ion channel complex. At concentrations between 10-7 and 10-5M both steroids inhibited binding of the convulsant t-butylbicyclophosphorothionate to the GABA-receptor complex and increased the binding of the benzodiazepine flunitrazepam; they also stimulated chloride uptake (as measured by uptake of 36Cl-) into isolated brain vesicles, and potentiated the inhibitory actions of GABA in cultured rat hippocampal and spinal cord neurons. These data may explain the ability of certain steroid hormones to rapidly alter neuronal excitability and may provide a mechanism for the anesthetic and hypnotic actions of naturally occurring and synthetic anesthetic steroids.

Original languageEnglish
Pages (from-to)1004-1007
Number of pages4
JournalScience
Volume232
Issue number4753
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

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    Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., & Paul, S. M. (1986). Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science, 232(4753), 1004-1007. https://doi.org/10.1126/science.2422758