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Published on: June 9, 2017

Non-genomic effects of progesterone on the signaling function of G protein-coupled receptors

K Burger1, F Fahrenholz, G Gimpl

  • 1Johannes Gutenberg-Universität Mainz, Institut für Biochemie, Becherweg 30, 55099, Mainz, Germany.

FEBS Letters
|December 28, 1999
PubMed

Insights

Progesterone rapidly and reversibly inhibits calcium signaling in various cell types by affecting G protein-coupled receptors. This non-genomic effect is cell-specific, not receptor-specific.

Area of Science:

  • Cell biology
  • Endocrinology
  • Pharmacology

Background:

  • G protein-coupled receptors (GPCRs) mediate cellular responses to various stimuli.
  • Calcium signaling is a critical intracellular pathway regulated by GPCRs.
  • Progesterone is a key steroid hormone with known genomic and non-genomic effects.

Purpose of the Study:

  • To investigate the non-genomic effects of progesterone on calcium signaling pathways.
  • To determine the specificity of progesterone's action on different G protein-coupled receptors and cell types.

Main Methods:

  • Calcium imaging assays were performed on multiple cell lines expressing various GPCRs.
  • Cells were stimulated with specific ligands to evoke calcium signaling.
  • The effects of varying concentrations of progesterone on ligand-evoked calcium responses were measured.
  • Experiments included assessments of reversibility and independence from protein synthesis (using cycloheximide).

Main Results:

  • Progesterone, at concentrations from 10 microM to 200 microM, modulated calcium signaling in response to GPCR stimulation.
  • A concentration of 160 microM progesterone completely abolished signaling across all tested receptors.
  • The inhibitory effect of progesterone was rapid and reversible.
  • The observed effects were not prevented by cycloheximide, indicating a non-genomic mechanism.
  • Progesterone's action demonstrated greater specificity towards cell types than specific receptors.

Conclusions:

  • Progesterone exerts rapid, non-genomic inhibitory effects on calcium signaling mediated by GPCRs.
  • The action of progesterone is cell-type specific rather than receptor-specific.
  • These findings contrast with previous reports suggesting a direct high-affinity interaction between progesterone and the oxytocin receptor.

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