Functional Estrogen Receptors of Red Blood Cells. Do They Influence Intracellular Signaling?

Rosa Vona, Lucrezia Gambardella, Elena Ortona, Maria Santulli, Walter Malorni, Alessandra Carè, Donatella Pietraforte, Elisabetta Straface

Research output: Contribution to journalArticlepeer-review


BACKGROUND/AIMS: Estrogen could play a key role in the mechanisms underlying sex-related disparity in the incidence of thrombotic events. We investigated whether estrogen receptors (ERs) were expressed in human red blood cells (RBCs), and if they affected cell signaling of erythrocyte constitutive isoform of endothelial NO-synthase (eNOS) and nitric oxide (NO) release.

METHODS: RBCs from 29 non-smoker volunteers (15 males and 14 females) aged between 20 and 40 years were analyzed by cytometry and western blot. In particular, content and distribution of ER-α and ER-β, tyrosine kinases and eNOS phosphorylation and NO release were analyzed.

RESULTS: We demonstrated that: i) both ER-α and ER-β were expressed by RBCs; ii) they were both functionally active; and iii) ERs distribution and function were different in males and females. In particular, ERs modulated eNOS phosphorylation and NO release in RBCs from both sexes, but they induced the phosphorylation of specific tyrosine residues of kinases linked to eNOS activation and NO release in the RBCs from females only.

CONCLUSION: Collectively, these data suggest that ERs could play a critical role in RBC intracellular signaling. The possible implication of this signaling in sex-linked risk disparity in human cardiovascular diseases, e.g. in thrombotic events, may not be ruled out.

Original languageEnglish
Pages (from-to)186-199
Number of pages14
JournalCellular Physiology and Biochemistry
Issue number1
Publication statusPublished - 2019


  • Adult
  • Dronabinol/pharmacology
  • Erythrocytes/cytology
  • Estrogen Receptor alpha/antagonists & inhibitors
  • Estrogen Receptor beta/antagonists & inhibitors
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1/metabolism
  • Mitogen-Activated Protein Kinase 3/metabolism
  • Nitric Oxide/metabolism
  • Nitric Oxide Synthase Type III/metabolism
  • Phosphorylation/drug effects
  • Piperidines/pharmacology
  • Proto-Oncogene Proteins c-akt/metabolism
  • Pyrazoles/pharmacology
  • Receptors, Estrogen/metabolism
  • Signal Transduction/drug effects
  • Young Adult


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