Progesterone modulates neuronal excitability bidirectionally. (23rd January 2021)

• Record Type: Journal Article
• Authors: Kapur, Jaideep; Joshi, Suchitra
• Is Part Of: Neuroscience letters. Volume 744(2021)
• Publication Date: 2021-01-23
• Subjects: Progesterone -- Progesterone receptors -- Allopregnanolone -- Catamenial epilepsy -- AMPA receptors -- GABA-A receptors; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135619
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Progesterone regulation of neuronal activity and seizures. Progesterone receptor activation exerts seizure-promoting effects. Progesterone receptor activation could contribute to catamenial seizure exacerbation. Allopregnanolone suppresses seizure activity through potentiation of GABAA receptors. Abstract: 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 (GABAA Rs). 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.