PT - JOURNAL ARTICLE AU - Paolo Follesa AU - Mariangela Serra AU - Elisabetta Cagetti AU - Maria Giuseppina Pisu AU - Stefania Porta AU - Stefania Floris AU - Federico Massa AU - Enrico Sanna AU - Giovanni Biggio TI - Allopregnanolone Synthesis in Cerebellar Granule Cells: Roles in Regulation of GABA<sub>A</sub> Receptor Expression and Function during Progesterone Treatment and Withdrawal DP - 2000 Jun 01 TA - Molecular Pharmacology PG - 1262--1270 VI - 57 IP - 6 4099 - http://molpharm.aspetjournals.org/content/57/6/1262.short 4100 - http://molpharm.aspetjournals.org/content/57/6/1262.full SO - Mol Pharmacol2000 Jun 01; 57 AB - Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of γ-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABAA receptor α1, α3, α5, and γ2 subunit mRNAs. These effects were accompanied by decreases in the efficacies of diazepam and the β-carboline DMCM with regard to modulation of GABA-evoked Cl− currents. Withdrawal from such progesterone treatment resulted in a rapid and selective increase in the abundance of the GABAA α4 subunit mRNA that was associated with a restoration of receptor sensitivity to the negative modulatory action of DMCM, a positive receptor response to flumazenil, and continued reduced responsiveness of receptors to diazepam. Prevention of allopregnanolone synthesis by the 5α-reductase inhibitor finasteride also prevented the changes in both GABAA receptor gene expression and receptor function elicited by progesterone treatment and withdrawal. The American Society for Pharmacology and Experimental Therapeutics