Cited by 59Estrogen and related hormone effectsNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

Membrane progesterone receptor beta (mPRβ/Paqr8) promotes progesterone-dependent neurite outgrowth in PC12 neuronal cells via non-G protein-coupled receptor (GPCR) signaling

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Kasubuchi, Mayu, Watanabe, Keita, Hirano, Kanako, Inoue, Daisuke, Li, Xuan, Terasawa, Kazuya, Konishi, Morichika, Itoh, Nobuyuki +1 more·2017·Scientific Reports

Abstract

Recently, sex steroid membrane receptors garnered world-wide attention because they may be related to sex hormone-mediated unknown rapid non-genomic action that cannot be currently explained by their genomic action via nuclear receptors. Progesterone affects cell proliferation and survival via non-genomic effects. In this process, membrane progesterone receptors (mPRα, mPRβ, mPRγ, mPRδ, and mPRε) were identified as putative G protein-coupled receptors (GPCRs) for progesterone. However, the structure, intracellular signaling, and physiological functions of these progesterone receptors are still unclear. Here, we identify a molecular mechanism by which progesterone promotes neurite outgrowth through mPRβ (Paqr8) activation. Mouse mPRβ mRNA was specifically expressed in the central nervous system. It has an incomplete GPCR topology, presenting 6 transmembrane domains and did not exhibit typical GPCR signaling. Progesterone-dependent neurite outgrowth was exhibited by the promotion of ERK phosphorylation via mPRβ, but not via other progesterone receptors such as progesterone membrane receptor 1 (PGRMC-1) and nuclear progesterone receptor in nerve growth factor-induced neuronal PC12 cells. These findings provide new insights of regarding the non-genomic action of progesterone in the central nervous system.

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Authors
Kasubuchi, M., Watanabe, K., Hirano, K., Inoue, D., Li, X., Terasawa, K., Konishi, M., Itoh, N., & Kimura, I.
Affiliations
  • Tokyo University of Agriculture and Technology (JP)
  • Kyoto University (JP)
  • Kobe Pharmaceutical University (JP)
Corresponding author
Kimura, Ikuo
Venue
Scientific Reports
Published
2017-07-12
Volume
7
Issue
1
Pages
5168-5168
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2725233258
Cited by
59
References
46
Citations by year
2026: 3 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 6 · 2018: 3
FWCI
2.53
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (JP16H01355, JP15H05344)
  • Cosmetology Research Foundation
  • Japan Society for the Promotion of Science (JP16H01355, 15H05344)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
progesterone, non-genomic steroid action, neurite outgrowth, PC12 cells, ERK1/2 phosphorylation, G protein-coupled receptor signaling, sex steroid receptors, central nervous system, nuclear progesterone receptor
MeSH terms
Neuronal Outgrowth, Animals, Neurons, Phosphorylation, Progesterone, Receptors, Progesterone, Signal Transduction, PC12 Cells, Phosphatidylinositol 3-Kinases, Nerve Growth Factor, Receptors, G-Protein-Coupled, Extracellular Signal-Regulated MAP Kinases, Rats

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