Progesterone-Independent Neurosteroid Regulation of Alpha2-GABA-A Receptors in the Hippocampus Subfields
March 2017
in “
Brain research
”
TLDR Progesterone and its byproducts control a specific receptor in the brain independently of progesterone receptors, affecting conditions related to the menstrual cycle.
The study investigated the role of progesterone (P) and its conversion to neurosteroids in regulating α2-subunit expression of GABA-A receptors in the hippocampus, which is important for understanding epilepsy and seizure susceptibility. The research used finasteride, a neurosteroid synthesis inhibitor, and progesterone receptor (PR) knockout mice to determine the influence of PRs on α2-subunit plasticity. The results showed that α2-subunit expression increased during the high-P state of the diestrous stage and with P treatment in both wildtype and PR knockout mice. However, when the conversion of P to neurosteroids was blocked by finasteride, there was no change in α2-subunit expression in either genotype. This indicates that P and neurosteroids regulate α2-GABA-A receptor expression in the hippocampus through a mechanism that does not involve PRs, which has implications for conditions related to the menstrual cycle.
