Edvinsson Jacob C A, Grubor Irena, Maddahi Aida, Edvinsson Lars
Department of Clinical Sciences, Faculty of Medicine, Lund University, Getingevagen 4, Lund, 22185, Sweden.
Department of Neurosurgery, University Hospital, Lund, Sweden.
J Headache Pain. 2024 Dec 11;25(1):216. doi: 10.1186/s10194-024-01933-w.
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.
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.
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.
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.
本研究旨在探讨在人类颅内动脉中，与偏头痛相关的血管舒缩反应以及激素和神经肽（血管加压素、催产素、雌激素、孕酮、睾酮、胰淀素、肾上腺髓质素和降钙素基因相关肽（CGRP））的受体定位是否存在性别差异。
本研究使用了人类大脑皮质动脉和脑膜中动脉。这些组织是在神经外科手术过程中切除并在获得同意后捐赠的。使用线肌动描记器记录动脉在暴露于激素或神经肽后的血管舒缩反应。进行免疫组织化学以检查其受体在人类颅内动脉中的表达和定位。
血管加压素显示出最强的收缩反应，其次是催产素和孕酮。与肾上腺髓质素、胰淀素、睾酮和雌激素相比，CGRP表现出最强的血管舒张反应。在雄性和雌性动脉的血管舒缩反应中未观察到显著差异。血管舒缩效应得到血管平滑肌细胞中相应受体存在的支持。雌激素受体（ERα和ERβ）、孕酮受体（PR）、血管加压素1a受体（V1aR）和催产素受体（OTR）在覆盖大脑皮质的脑动脉壁和硬脑膜的颅内动脉中均有表达。发现ERα、V1aR和PR定位于平滑肌细胞和内皮细胞中，而OTR仅位于平滑肌细胞内。
下丘脑、性激素和胰腺激素（胰淀素）受体在人类颅内动脉壁中表达。血管舒缩反应未显示出性别差异，然而，当汇总两性数据时，与大脑皮质动脉相比，脑膜中动脉对血管加压素的收缩反应更高且更强。总体而言，在月经开始时循环水平下降的激素雌激素、孕酮和催产素与CGRP相比仅表现出适度的血管舒缩反应。这表明它们在诱发月经性偏头痛发作中的作用与血管舒缩反应没有直接关系。
