Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

PLoS One. 2016 Aug 5;11(8):e0159640. doi: 10.1371/journal.pone.0159640. eCollection 2016.

Abstract

The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30.

MeSH terms

  • Animals
  • Benzaldehydes / pharmacology
  • Cyclic AMP / metabolism
  • Estradiol / pharmacology*
  • Evoked Potentials / drug effects*
  • Female
  • High-Throughput Nucleotide Sequencing
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / metabolism
  • Olfactory Receptor Neurons / drug effects
  • Olfactory Receptor Neurons / metabolism*
  • Patch-Clamp Techniques
  • Progesterone / pharmacology*
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Sequence Analysis, RNA

Substances

  • Benzaldehydes
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Progesterone
  • Estradiol
  • RNA
  • vanillin
  • Cyclic AMP
  • benzaldehyde

Grants and funding

Hanns Hatt was funded by the DFG-Sonderforschungsbereich 642 “GTP- and ATP dependent membrane processes”. The authors acknowledge support by the Open Access Publication Funds of the Ruhr-Universität Bochum. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripts.