3alpha-hydroxy-5alpha-pregnan-20-one exposure reduces GABA(A) receptor alpha4 subunit mRNA levels.
To examine the direct effects of neurosteroids on gamma-aminobutyric acid type A (GABA(A)) receptor expression, we exposed developing neuronal cells (P19) in vitro to 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP, allopregnanolone). Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed a concentration-dependent decrease in GABA(A) receptor alpha4 subunit mRNA expression that reversed 24 h after steroid withdrawal. These data suggest that variations in neurosteroid levels regulate the pattern of GABA(A) receptor subunit expression and may alter the trophic effects of GABA.
Grobin
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AC
Department of Psychiatry, Pharmacology and Bowles Center for Alcohol Studies, CB #7178, University of North Carolina at Chapel Hill, NC 27599-7178, USA. grobinac@med.unc.edu
Morrow
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AL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D011280:Pregnanolone / Q000494:pharmacology*; D021122:Protein Subunits; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000235:genetics*; D014407:Tumor Cells, Cultured
D021122:Protein Subunits; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011280:Pregnanolone