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

Sci Rep. 2017 Jul 12;7(1):5168. doi: 10.1038/s41598-017-05423-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / pharmacology
  • Neuronal Outgrowth* / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism*
  • PC12 Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Progesterone / metabolism*
  • Progesterone / pharmacology
  • Rats
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Progesterone / agonists
  • Receptors, Progesterone / metabolism*
  • Signal Transduction / drug effects


  • Receptors, G-Protein-Coupled
  • Receptors, Progesterone
  • adipoQ receptor 8, rat
  • progesterone receptor B
  • Progesterone
  • Nerve Growth Factor
  • Phosphatidylinositol 3-Kinases
  • Extracellular Signal-Regulated MAP Kinases