Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Estrogen receptors α, β and GPER in the CNS and trigeminal system - molecular and functional aspects

Research output: Contribution to journalJournal articleResearchpeer-review

  1. PACAP38 and PAC receptor blockade: a new target for headache?

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Cilostazol induced migraine does not respond to sumatriptan in a double blind trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Repair-related molecular changes during recovery phase of ischemic stroke in female rats

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Changes in P2Y6 receptor-mediated vasoreactivity following focal and global ischemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Ny medicin beskytter hjernen ved voldsomme hjerneblødninger hos rotter og hunde - nu bliver den testet på danske patienter

    Research output: Contribution to journalContribution to newspaper - Newspaper articleCommunication

  4. Dual action of the cannabinoid receptor 1 ligand arachidonyl-2'-chloroethylamide on calcitonin gene-related peptide release

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Lasmiditan and 5-Hydroxytryptamine in the rat trigeminal system; expression, release and interactions with 5-HT1 receptors

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

BACKGROUND: Migraine occurs 2-3 times more often in females than in males and is in many females associated with the onset of menstruation. The steroid hormone, 17β-estradiol (estrogen, E2), exerts its effects by binding and activating several estrogen receptors (ERs). Calcitonin gene-related peptide (CGRP) has a strong position in migraine pathophysiology, and interaction with CGRP has resulted in several successful drugs for acute and prophylactic treatment of migraine, effective in all age groups and in both sexes.

METHODS: Immunohistochemistry was used for detection and localization of proteins, release of CGRP and PACAP investigated by ELISA and myography/perfusion arteriography was performed on rat and human arterial segments.

RESULTS: ERα was found throughout the whole brain, and in several migraine related structures. ERβ was mainly found in the hippocampus and the cerebellum. In trigeminal ganglion (TG), ERα was found in the nuclei of neurons; these neurons expressed CGRP or the CGRP receptor in the cytoplasm. G-protein ER (GPER) was observed in the cell membrane and cytoplasm in most TG neurons. We compared TG from males and females, and females expressed more ER receptors. For neuropeptide release, the only observable difference was a baseline CGRP release being higher in the pro-estrous state as compared to estrous state. In the middle cerebral artery (MCA), we observed similar dilatory ER-responses between males and females, except for vasodilatory ERβ which we observed only in female arteries.

CONCLUSION: These data reveal significant differences in ER receptor expression between male and female rats. This contrasts to CGRP and PACAP release where we did not observe discernable difference between the sexes. Together, this points to a hypothesis where estrogen could have a modulatory role on the trigeminal neuron function in general rather than on the acute CGRP release mechanisms and vasomotor responses.

Original languageEnglish
Article number131
JournalJournal of Headache and Pain
Volume21
Issue number1
Pages (from-to)131
ISSN1129-2369
DOIs
Publication statusPublished - Dec 2020

    Research areas

  • Animals, Calcitonin Gene-Related Peptide/metabolism, Central Nervous System/metabolism, Estrogen Receptor alpha/metabolism, Estrogen Receptor beta/metabolism, Female, Humans, Male, Migraine Disorders/physiopathology, Neurons/metabolism, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism, Rats, Rats, Sprague-Dawley, Receptors, Calcitonin Gene-Related Peptide/metabolism, Signal Transduction, Trigeminal Ganglion/metabolism, Immunohistochemistry, Myography, Brain, PACAP, Estrogen receptors, MCA, Trigeminal ganglion, CGRP

ID: 61421485