Allopregnanolone and regulation of GABA-A plasticity

[xptriado]

ncbi.nlm.nih.gov/pubmed/11744076 —> Anyone has access to this study?
Title: Role of allopregnanolone in regulation of GABA(A) receptor plasticity during long-term exposure to and withdrawal from progesterone.

Neuroactive steroids such as 3alpha,5alpha-TH PROG might thus exert differential actions on GABA(A) receptor plasticity in distinct neuronal cell populations

ncbi.nlm.nih.gov/pubmed/20883478
Title: Tolerance to allopregnanolone with focus on the GABA-A receptor.

We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the ventral-posteriomedial nucleus of the thalamus.

ncbi.nlm.nih.gov/pubmed/7968353
Title: Chronic GABA treatment downregulates the GABAA receptor alpha 2 and alpha 3 subunit mRNAS as well as polypeptide expression in primary cultured cerebral cortical neurons.

ncbi.nlm.nih.gov/pubmed/8883948
Title: Down-regulation of the GABA receptor subunits mRNA levels in mammalian cultured cortical neurons following chronic neurosteroid treatment.

[xptriado]

Guys, could this be the missing link?
I’d like to call your attention to this study:

ncbi.nlm.nih.gov/pubmed/16879715
Title: Changes in expression of the delta subunit of the GABA (A) receptor and in receptor function induced by progesterone exposure and withdrawal.

Progesterone treatment for 1 day increased the amounts of both delta subunit mRNA and protein, whereas such treatment for 6 days induced marked decreases in the abundance of both the mRNA and protein. Subsequent progesterone withdrawal up-regulated expression of the delta subunit, which was significantly increased at 9-12 h after withdrawal. These effects of progesterone were mimicked by 3alpha,5alpha-THPROG and blocked by the 5alpha-reductase inhibitor finasteride. They were also accompanied by parallel changes in the function of GABA(A) receptors in hippocampal neurons.

This could be the reason why progesterone dosing and sudden withdrawal is working for some…and it has nothing to do with Progesterone receptors but in fact with GABA-A receptors!