Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries

Abstract Background The purpose of this study was to examine whether there are sex differences in vasomotor responses and receptor localization of hormones and neuropeptides with relevance to migraine (vasopressin, oxytocin, estrogen, progesterone, testosterone, amylin, adrenomedullin and calcitonin...

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Main Authors: Jacob C. A. Edvinsson, Irena Grubor, Aida Maddahi, Lars Edvinsson
Format: Article
Language:English
Published: BMC 2024-12-01
Series:The Journal of Headache and Pain
Subjects:
Online Access:https://doi.org/10.1186/s10194-024-01933-w
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author Jacob C. A. Edvinsson
Irena Grubor
Aida Maddahi
Lars Edvinsson
author_facet Jacob C. A. Edvinsson
Irena Grubor
Aida Maddahi
Lars Edvinsson
author_sort Jacob C. A. Edvinsson
collection DOAJ
description Abstract Background The purpose of this study was to examine whether there are sex differences in vasomotor responses and receptor localization of hormones and neuropeptides with relevance to migraine (vasopressin, oxytocin, estrogen, progesterone, testosterone, amylin, adrenomedullin and calcitonin gene-related peptide (CGRP)) in human intracranial arteries. Methods Human cortical cerebral and middle meningeal arteries were used in this study. The tissues were removed in conjunction with neurosurgery and donated with consent. Vasomotor responses of arteries, after exposure to hormones or neuropeptides, were recorded using a wire myograph. Immunohistochemistry was performed to examine the expression and localization of their receptors within human intracranial arteries. Results Vasopressin showed the strongest contractile responses, followed by oxytocin and progesterone. CGRP displayed the strongest vasodilatory response when compared to adrenomedullin, amylin, testosterone and estrogen. No significant differences were observed in vasomotor responses between male and female arteries. The vasomotor effects were supported by the presence of corresponding receptors in the vascular smooth muscle cells. Estrogen receptors (ERα and ERβ), progesterone receptor (PR), vasopressin 1a receptor (V1aR), and the oxytocin receptor (OTR) were expressed in the walls of both cerebral arteries overlying the cerebral cortex and intracranial arteries of the dura mater. ERα, V1aR, and PR were found to be localized in both smooth muscle cells and endothelium, whereas OTR was exclusively located within the smooth muscle cells. Conclusions Hypothalamic, sex hormones and the pancreas hormone (amylin) receptors are expressed in the human intracranial artery walls. The vasomotor responses revealed no sex differences, however contractile responses to vasopressin was higher and more potent in MMA compared to CCA when pooling data from both sexes. Overall, the hormones estrogen, progesterone and oxytocin, which drop in circulating levels at onset of menstruation, only showed modest vasomotor responses as compared to CGRP. This suggests that their role in inducing menstrual migraine attacks is not directly related to vasomotor responses. Graphical Abstract
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spelling doaj-art-c5970dd368e3427ea2bc7db34b5f9b192025-08-20T02:37:57ZengBMCThe Journal of Headache and Pain1129-23772024-12-0125111310.1186/s10194-024-01933-wMale-female comparison of vasomotor effects of circulating hormones in human intracranial arteriesJacob C. A. Edvinsson0Irena Grubor1Aida Maddahi2Lars Edvinsson3Department of Clinical Sciences, Faculty of Medicine, Lund UniversityDepartment of Neurosurgery, University HospitalDepartment of Clinical Sciences, Faculty of Medicine, Lund UniversityDepartment of Clinical Sciences, Faculty of Medicine, Lund UniversityAbstract Background The purpose of this study was to examine whether there are sex differences in vasomotor responses and receptor localization of hormones and neuropeptides with relevance to migraine (vasopressin, oxytocin, estrogen, progesterone, testosterone, amylin, adrenomedullin and calcitonin gene-related peptide (CGRP)) in human intracranial arteries. Methods Human cortical cerebral and middle meningeal arteries were used in this study. The tissues were removed in conjunction with neurosurgery and donated with consent. Vasomotor responses of arteries, after exposure to hormones or neuropeptides, were recorded using a wire myograph. Immunohistochemistry was performed to examine the expression and localization of their receptors within human intracranial arteries. Results Vasopressin showed the strongest contractile responses, followed by oxytocin and progesterone. CGRP displayed the strongest vasodilatory response when compared to adrenomedullin, amylin, testosterone and estrogen. No significant differences were observed in vasomotor responses between male and female arteries. The vasomotor effects were supported by the presence of corresponding receptors in the vascular smooth muscle cells. Estrogen receptors (ERα and ERβ), progesterone receptor (PR), vasopressin 1a receptor (V1aR), and the oxytocin receptor (OTR) were expressed in the walls of both cerebral arteries overlying the cerebral cortex and intracranial arteries of the dura mater. ERα, V1aR, and PR were found to be localized in both smooth muscle cells and endothelium, whereas OTR was exclusively located within the smooth muscle cells. Conclusions Hypothalamic, sex hormones and the pancreas hormone (amylin) receptors are expressed in the human intracranial artery walls. The vasomotor responses revealed no sex differences, however contractile responses to vasopressin was higher and more potent in MMA compared to CCA when pooling data from both sexes. Overall, the hormones estrogen, progesterone and oxytocin, which drop in circulating levels at onset of menstruation, only showed modest vasomotor responses as compared to CGRP. This suggests that their role in inducing menstrual migraine attacks is not directly related to vasomotor responses. Graphical Abstracthttps://doi.org/10.1186/s10194-024-01933-wEstrogenOxytocinVasopressinProgesteroneTestosteroneAdrenomedullin
spellingShingle Jacob C. A. Edvinsson
Irena Grubor
Aida Maddahi
Lars Edvinsson
Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
The Journal of Headache and Pain
Estrogen
Oxytocin
Vasopressin
Progesterone
Testosterone
Adrenomedullin
title Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
title_full Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
title_fullStr Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
title_full_unstemmed Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
title_short Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries
title_sort male female comparison of vasomotor effects of circulating hormones in human intracranial arteries
topic Estrogen
Oxytocin
Vasopressin
Progesterone
Testosterone
Adrenomedullin
url https://doi.org/10.1186/s10194-024-01933-w
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AT aidamaddahi malefemalecomparisonofvasomotoreffectsofcirculatinghormonesinhumanintracranialarteries
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