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慢性皮质酮暴露会引起雄性大鼠的瘙痒过敏和性功能障碍:脊髓中两个不同的胃泌素释放肽系统之间的关系。

Chronic corticosterone exposure evokes itch hypersensitivity and sexual dysfunction in male rats: Relationship between the two distinct gastrin-releasing peptide systems in the spinal cord.

机构信息

Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan; Mouse Genomics Resources Laboratory, National Institute of Genetics, Yata, Mishima, Shizuoka 411-8540, Japan; Department of Environmental Health, Faculty of Human Life and Environmental Sciences, Nara Women's University, Kitauoya Nishimachi, Nara 630-8506, Japan.

Ushimado Marine Institute (UMI), Graduate School of Natural Science and Technology, Okayama University, Ushimado, Setouchi, Okayama 701-4303, Japan.

出版信息

Gen Comp Endocrinol. 2023 Aug 1;339:114289. doi: 10.1016/j.ygcen.2023.114289. Epub 2023 Apr 23.

Abstract

In today's society, people are subjected to many social stressors, and excessive chronic stress causes functional disruption of the neuroendocrine system and many diseases. Although the exacerbation of atopic dermatitis with symptoms of itching and erectile dysfunction is induced by chronic stress, the details of the mechanisms are unknown. Here, we examined the effects of chronic stress on itch sensation and male sexual function at the behavioral and molecular levels, focusing on two distinct gastrin-releasing peptide (GRP) systems that independently regulate itch transmission, i.e., the somatosensory GRP system, and male sexual function, i.e., the lumbosacral autonomic GRP system, in the spinal cord. In a rat model of chronic stress induced by chronic corticosterone (CORT) administration, we observed increased plasma CORT concentrations, decreased body weight, and increased anxiety-like behavior, similar to that observed in humans. Chronic CORT exposure induced hypersensitivity to itch and increased the Grp mRNA level in the spinal somatosensory system, but there was no change in pain or tactile sensitivity. Antagonists of the somatosensory GRP receptor, an itch-specific mediator, suppressed itch hypersensitivity induced by chronic CORT exposure. In contrast, chronic CORT exposure decreased male sexual behavior, ejaculated semen volume, vesicular gland weight, and plasma testosterone levels. However, there were no effects on the expression of Grp mRNA or protein in the lumbosacral autonomic GRP system, which regulates male sexual function. In summary, chronic stress model rats showed itch hypersensitivity and impaired sexual function in males, and the involvement of the spinal GRP systems was apparent in itch hypersensitivity.

摘要

在当今社会,人们承受着许多社会压力源,过度的慢性压力会导致神经内分泌系统功能紊乱和许多疾病。尽管特应性皮炎的症状(瘙痒和勃起功能障碍)加剧是由慢性应激引起的,但机制的细节尚不清楚。在这里,我们在行为和分子水平上检查了慢性应激对瘙痒感和男性性功能的影响,重点关注独立调节瘙痒传递的两个不同的胃泌素释放肽(GRP)系统,即躯体感觉 GRP 系统,和男性性功能,即腰骶自主 GRP 系统,在脊髓中。在慢性皮质酮(CORT)给药诱导的慢性应激大鼠模型中,我们观察到血浆 CORT 浓度升高、体重减轻和焦虑样行为增加,类似于人类观察到的情况。慢性 CORT 暴露诱导瘙痒敏感性增加,并且脊髓体感觉系统中的 Grp mRNA 水平增加,但疼痛或触觉敏感性没有变化。躯体感觉 GRP 受体拮抗剂,一种特异性瘙痒介质,可抑制慢性 CORT 暴露引起的瘙痒敏感性增加。相比之下,慢性 CORT 暴露会降低雄性性行为、射精量、精囊重量和血浆睾酮水平。然而,对调节男性性功能的腰骶自主 GRP 系统中的 Grp mRNA 或蛋白质表达没有影响。总之,慢性应激模型大鼠表现出瘙痒敏感性增加和雄性性功能障碍,脊髓 GRP 系统参与了瘙痒敏感性增加。

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