Progesterone modulates neuronal excitability bidirectionally

Neurosci Lett. 2021 Jan 23:744:135619. doi: 10.1016/j.neulet.2020.135619. Epub 2021 Jan 6.


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

Keywords: AMPA receptors; Allopregnanolone; Catamenial epilepsy; GABA-A receptors; Progesterone; Progesterone receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / metabolism*
  • Anticonvulsants / therapeutic use
  • Epilepsy / drug therapy
  • Epilepsy / metabolism*
  • GABA-A Receptor Antagonists / pharmacology
  • GABA-A Receptor Antagonists / therapeutic use
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism*
  • Progesterone / metabolism*
  • Progesterone / therapeutic use
  • Receptors, GABA-A / metabolism*
  • Receptors, Progesterone / metabolism*


  • Anticonvulsants
  • GABA-A Receptor Antagonists
  • Receptors, GABA-A
  • Receptors, Progesterone
  • Progesterone