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Many or too many progesterone membrane receptors?: clinical implications

Several receptors for nongenomically initiated actions of progesterone (P4) exist, namely membrane-associated P4 receptors (MAPRs), membrane progestin receptors (mPRs), receptors for neurosteroids [GABAA receptor (GABAAR), NMDA receptor, sigma-1 and -2 receptors (S1R/S2R)], the classical genomic P4...

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Bibliographic Details
Main Authors: Wendler, Alexandra (Author) , Wehling, Martin (Author)
Format: Article (Journal)
Language:English
Published: 14 November 2022
In: Trends in endocrinology and metabolism
Year: 2022, Volume: 33, Issue: 12, Pages: 850-868
ISSN:1879-3061
DOI:10.1016/j.tem.2022.10.001
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.tem.2022.10.001
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1043276022001795
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Author Notes:Alexandra Wendler and Martin Wehling
Description
Summary:Several receptors for nongenomically initiated actions of progesterone (P4) exist, namely membrane-associated P4 receptors (MAPRs), membrane progestin receptors (mPRs), receptors for neurosteroids [GABAA receptor (GABAAR), NMDA receptor, sigma-1 and -2 receptors (S1R/S2R)], the classical genomic P4 receptor (PGR), and α/β hydrolase domain-containing protein 2 (ABHD2). Two drugs related to this field have been approved: brexanolone (Zulresso™) for the treatment of postpartum depression, and ganaxolone (Ztalmy™) for the treatment of CDKL5 deficiency disorder. Both are derivatives of P4 and target the GABAAR. Several other indications are in clinical testing. CT1812 (Elayta™) is also being tested for the treatment of Alzheimer’s disease (AD) in Phase 2 clinical trials, targeting the P4 receptor membrane component 1 (PGRMC1)/S2R complex. In this Review, we highlight emerging knowledge on the mechanisms of nongenomically initiated actions of P4 and its derivatives.
Item Description:Gesehen am 18.01.2023
Physical Description:Online Resource
ISSN:1879-3061
DOI:10.1016/j.tem.2022.10.001

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