Progesterone modulates neuronal excitability bidirectionally

Progesterone acts on neurons directly by activating its receptor and through metabolic conversion to neumsteroids. There is emerging evidence that progesterone exerts excitatory effects by activating its cognate receptors (progesterone receptors, PRs) through enhanced expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole pmpionic acid receptors (AMPARs). Progesterone metabolite 5 alpha,3 alpha-tetrahydro-progesterone (allopregnanolone, THP) mediates its anxiolytic and sedative actions through the potentiation of synaptic and extrasynaptic gamma-aminobutyric acid type-A receptors (GABA(A)Rs). Here, we review progesterone's neummodulatory actions exerted through PRs and THP and their opposing role in regulating seizures, catamenial epilepsy, and seizure exacerbation associated with progesterone withdrawal.

Automated summary

Progesterone acts on neurons by activating its receptor and converting to neurosteroids, enhancing the expression of AMPARs. Its metabolite allopregnanolone mediates anxiolytic and sedative effects through enhanced GABA(A)Rs activation, showing opposing roles in regulating seizures and catamenial epilepsy.