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

Autor: Warfvinge K; Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden., Krause DN; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.; Department of Pharmacology, School of Medicine, University of California at Irvine, Irvine, CA, USA., Maddahi A; Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark., Edvinsson JCA; Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Edvinsson L; Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark. lars.edvinsson@med.lu.se.; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden. lars.edvinsson@med.lu.se.; Department of Internal Medicine, Lund University Hospital, S-22185, Lund, Sweden. lars.edvinsson@med.lu.se., Haanes KA; Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Jazyk: angličtina
Zdroj: The journal of headache and pain [J Headache Pain] 2020 Nov 10; Vol. 21 (1), pp. 131. Date of Electronic Publication: 2020 Nov 10.
DOI: 10.1186/s10194-020-01197-0
Abstrakt: 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.
Databáze: MEDLINE
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