Contribution of sex hormones to the sexually dimorphic response of colorectal motility to noxious stimuli in rats
Contribution of sex hormones to the sexually dimorphic response of colorectal motility to noxious stimuli in rats
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性激素对大鼠结直肠运动对有害刺激的性二态性反应的贡献
DOI：
10.1152/ajpgi.00033.2022
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发表时间：
2022
影响因子：
4.5
通讯作者：
Shimizu Yasutake
中科院分区：
文献类型：
--
作者：
Horii Kazuhiro;Sawamura Tomoya;Onishi Ayaka;Yuki Natsufu;Naitou Kiyotada;Shiina Takahiko;Shimizu Yasutake
我们最近的研究表明，结直肠中的有害刺激可通过雄性大鼠的大脑和脊髓排便中心增强结直肠运动。然而，在雌性大鼠中，有害刺激对结直肠运动没有影响。本研究的目的是确定性激素是否是脊髓排便中枢神经成分性别依赖性差异的主要影响因素。在氯胺酮和α-氯醛糖麻醉下，使用体内方法测量大鼠的结直肠运动。将辣椒素作为有害刺激物注入结直肠腔。雄性大鼠睾丸切除术对辣椒素诱导的结直肠运动反应没有影响。然而，在切除卵巢的雌性大鼠中，施用辣椒素增强了结直肠运动，尽管完整的雌性动物并未表现出增强的运动性。当使用缓释制剂对切除卵巢的雌性大鼠施用雌二醇时，除非将GABA A 受体拮抗剂鞘内施用至腰骶脊髓，否则施用辣椒素不会增强结直肠运动。这些发现表明，雌二醇允许 GABA 能神经元响应结肠内施用辣椒素而发挥作用。只有通过睾丸切除术消除雄性性激素的影响，雌二醇作用的GABA能抑制作用才能在雄性大鼠中显现出来。总而言之，我们的结果表明，性激素通过调节 GABA 能途径，促进结直肠运动增强中的性二态性反应，以响应有害刺激。新的和值得注意的这项研究表明，雌二醇不仅可以在雌性大鼠中进行抑制性调节，而且可以在睾丸切除的雄性大鼠中进行脊髓排便中枢的抑制性调节。 GABA 能途径可能与雌二醇的作用有关。这是第一份表明性激素通过改变调节途径的神经成分影响结直肠运动的报告。我们的研究结果为与性激素变化相关的排便障碍的病理生理机制提供了新的见解。
Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this study was to determine whether sex hormones are major contributing factors for sex-dependent differences in neural components of the spinal defecation center. Colorectal motility was measured using an in vivo method under ketamine and α-chloralose anesthesia in rats. Capsaicin was administered into the colorectal lumen as noxious stimuli. Orchiectomy in male rats had no effect on the capsaicin-induced response of colorectal motility. However, in ovariectomized female rats, capsaicin administration enhanced colorectal motility, though intact female animals did not show enhanced motility. When estradiol was administered by using a sustained-release preparation in ovariectomized female rats, capsaicin administration did not enhance colorectal motility unless a GABAAreceptor antagonist was intrathecally administered to the lumbosacral spinal cord. These findings suggest that estradiol allowed the GABAergic neurons to operate in response to intracolonic administration of capsaicin. The operation of GABAergic inhibition by the action of estradiol could be manifested in male rats only when the effects of male sex hormones were removed by orchiectomy. Taken together, our results indicate that sex hormones contribute to the sexually dimorphic response in colorectal motility enhancement in response to noxious stimuli through modulating GABAergic pathways.NEW & NOTEWORTHYThis study demonstrated that estradiol permits inhibitory regulation in the spinal defecation center not only in female rats but also in orchiectomized male rats. GABAergic pathways are likely involved in the effect of estradiol. This is the first report showing that sex hormones affect colorectal motility through the alteration of neural components of the regulatory pathways. Our findings provide a novel insight into pathophysiological mechanisms of defecation disorders related to changes in sex hormones.