@article {Follesa1262, author = {Paolo Follesa and Mariangela Serra and Elisabetta Cagetti and Maria Giuseppina Pisu and Stefania Porta and Stefania Floris and Federico Massa and Enrico Sanna and Giovanni Biggio}, title = {Allopregnanolone Synthesis in Cerebellar Granule Cells: Roles in Regulation of GABAA Receptor Expression and Function during Progesterone Treatment and Withdrawal}, volume = {57}, number = {6}, pages = {1262--1270}, year = {2000}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {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}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/57/6/1262}, eprint = {https://molpharm.aspetjournals.org/content/57/6/1262.full.pdf}, journal = {Molecular Pharmacology} }