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

Edvinsson, Jacob C A LU ; Grubor, Irena LU ; Maddahi, Aida LU and Edvinsson, Lars LU (2024) In Journal of Headache and Pain 25.
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... (More)

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.

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; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Female, Male, Middle Aged, Cerebral Arteries/drug effects, Sex Characteristics, Adult, Oxytocin/metabolism, Aged, Meningeal Arteries/drug effects, Hormones/blood, Vasopressins/metabolism, Vasomotor System/drug effects
in
Journal of Headache and Pain
volume
25
article number
216
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85211640150
  • pmid:39663536
ISSN
1129-2369
DOI
10.1186/s10194-024-01933-w
language
English
LU publication?
yes
id
900ae7f3-fda7-48ad-b45e-530dd8eb3fc7
date added to LUP
2024-12-12 08:21:24
date last changed
2025-07-10 00:26:59
@article{900ae7f3-fda7-48ad-b45e-530dd8eb3fc7,
  abstract     = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
  author       = {{Edvinsson, Jacob C A and Grubor, Irena and Maddahi, Aida and Edvinsson, Lars}},
  issn         = {{1129-2369}},
  keywords     = {{Humans; Female; Male; Middle Aged; Cerebral Arteries/drug effects; Sex Characteristics; Adult; Oxytocin/metabolism; Aged; Meningeal Arteries/drug effects; Hormones/blood; Vasopressins/metabolism; Vasomotor System/drug effects}},
  language     = {{eng}},
  month        = {{12}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Headache and Pain}},
  title        = {{Male-female comparison of vasomotor effects of circulating hormones in human intracranial arteries}},
  url          = {{http://dx.doi.org/10.1186/s10194-024-01933-w}},
  doi          = {{10.1186/s10194-024-01933-w}},
  volume       = {{25}},
  year         = {{2024}},
}