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

Published

Journal Article

Two metabolites of the steroid hormones progesterone and deoxycorticosterone, 3 alpha-hydroxy-5 alpha-dihydroprogesterone and 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone, are potent barbiturate-like ligands of the gamma-aminobutyric acid (GABA) receptor-chloride ion channel complex. At concentrations between 10(-7) and 10(-5)M 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.

Full Text

Duke Authors

Cited Authors

  • Majewska, MD; Harrison, NL; Schwartz, RD; Barker, JL; Paul, SM

Published Date

  • May 1986

Published In

Volume / Issue

  • 232 / 4753

Start / End Page

  • 1004 - 1007

PubMed ID

  • 2422758

Pubmed Central ID

  • 2422758

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.2422758

Language

  • eng