Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine
Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine
复制标题
DOI：
10.1007/s00221-020-05923-7
复制
发表时间：
2020-09-13
影响因子：
2
通讯作者：
Ogun, Muhammed Nur
中科院分区：
文献类型：
--
作者：
Cetinkaya, Ayhan;Kilinc, Erkan;Ogun, Muhammed Nur
包括降钙素基因相关肽（CGRP）和P物质（SP）释放在内的神经源性炎症在偏头痛发病机制中起着关键作用。女性偏头痛的患病率比男性高3倍，但其潜在机制仍不清楚。我们研究了雌性激素雌激素和孕激素对CGRP和SP在体内和体外的影响，在两种性别的大鼠。在体内实验中，将雄性、雌性和去卵巢大鼠分为四组（n = 7），分别为对照组、雌激素组、孕激素组和雌激素+孕激素组。各组分别每日腹腔内接受媒介物、17 β-雌二醇、孕酮和17 β-雌二醇+孕酮，持续5天。对于两种性别的离体实验，将分离的三叉神经节和半颅骨制备物分别分为四组（n = 6或8）作为体内组，并给予相同的供试品。采用ELISA法测定血浆和灌流液中CGRP和SP含量。在体内实验中，17 β-雌二醇降低了雄性大鼠的CGRP水平和卵巢切除大鼠的SP水平。黄体酮增加女性的CGRP和SP水平。他们的组合降低CGRP和SP水平的男性，只有SP水平的卵巢切除大鼠。在离体实验中，17 β-雌二醇减少了三叉神经节中男性的CGRP释放和女性的SP释放。而孕酮增加三叉神经节CGRP的释放，它减少SP释放从两种性别的半球头骨。它们的组合恢复了两种性别的三叉神经节和半球脑中孕酮介导的神经肽释放变化。雌激素通过调节CGRP和SP的释放来减轻神经源性炎症。在与偏头痛相关的不同部位，预后对这些神经肽具有双重作用。
Neurogenic inflammation including calcitonin gene-related peptide (CGRP) and substance-P (SP) release plays a pivotal role in migraine pathogenesis. Prevalence of migraine is similar to 3 folds higher in women than in men, but its underlying mechanisms remained unclear. We investigated the effects of female sex hormones estrogen and progesterone on CGRP and SP in in-vivo and ex-vivo in rats of both sexes. For in-vivo experiments, male, female and ovariectomized rats were separated into four groups (n = 7) as control, estrogen, progesterone and estrogen + progesterone, respectively. Groups received daily intraperitoneal vehicle, 17 beta-estradiol, progesterone and 17 beta-estradiol + progesterone for 5 days, respectively. For ex-vivo experiments in both sexes, isolated trigeminal ganglia and hemiskull preparations were divided into four groups (n = 6 or 8), respectively, as in-vivo groups, and administered the same test substances. CGRP and SP contents in plasma and superfusates were determined using ELISA. In in-vivo experiments, 17 beta-estradiol decreased CGRP levels in males and SP levels in ovariectomized rats. Progesterone increased both CGRP and SP levels in females. Their combination decreased both CGRP and SP levels in males, and only SP levels in ovariectomized rats. In ex-vivo experiments, 17 beta-estradiol reduced CGRP release in males and SP release in females in trigeminal ganglia. While progesterone increased CGRP release in trigeminal ganglia, it reduced SP release from hemiskulls in both sexes. Their combination restored progesterone-mediated changes in neuropeptides releases in both trigeminal ganglia and hemiskulls in both sexes. Estrogen alleviates neurogenic inflammation through modulation of CGRP and SP release. Progesterone has dual effects on these neuropeptides in different sites associated with migraine pain.