Gender differences in the effect of prenatal alcohol exposure on the hypothalamic-pituitary-adrenal axis response to immune signals
Gender differences in the effect of prenatal alcohol exposure on the hypothalamic-pituitary-adrenal axis response to immune signals
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DOI：
10.1016/0306-4530(95)00038-0
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发表时间：
1996-02-01
影响因子：
3.7
通讯作者：
Rivier, C
中科院分区：
文献类型：
--
作者：
Lee, S;Rivier, C
酒精 (E) 喂养的未成熟（3 周龄）大鼠后代对白细胞介素 1 β (IL-1 β) 和内毒素 (LPS) 等免疫信号的 ACTH 反应减弱。相比之下，成熟的后代通过过度激活下丘脑-垂体-肾上腺（HPA）轴来应对物理压力。目前的工作旨在确定产前 E 暴露对 HPA 轴对各种应激源的反应是否存在差异影响，或者性成熟是否改变了这些反应。当在 5 周龄时给予 IL-1 beta 时，与对照 (C) 或配对喂养 (PF) 动物相比，E 处理的完整雄性后代释放出较少的 ACTH。然而，它们表现出对脂多糖的增强反应以及松节油注射诱导的局部炎症过程。在同一年龄，与 C 或 PF 后代相比，完整的 E 雌性在对 IL-1 β、LPS 和松节油的反应中分泌的 ACTH 显着增加。到 9 周龄时，E 雄性和 E 雌性对所有三种免疫刺激都表现出更大的 (p < .05) ACTH 反应。为了确定性类固醇是否调节 E 对女性的影响，在青春期之前进行了卵巢切除术。这种治疗减少了 E 和 C 大鼠响应 IL-1 beta、LPS 和松节油释放的 ACTH 差异。这些结果表明，虽然产前暴露于 E 的未成熟大鼠响应细胞因子释放的 ACTH 少于 C 或 PF 动物，但这种反应在青春期后发生了质的逆转。当时，与其他组相比，E 后代分泌的 ACTH 量较多，这让人想起当这些后代受到身体压力时，HPA 轴的过度活跃反应。有趣的是，去除循环卵巢类固醇可以防止E的影响发挥出来。这表明受产前 E 影响的途径与受女性性类固醇影响的途径之间存在功能关系，这对于调节 HPA 轴的活动非常重要。版权所有 (C) 1996 爱思唯尔科学有限公司
Immature (3 week old) rat offspring of alcohol (E)-fed dams show a blunted ACTH response to immune signals such as interleukin-1 beta (IL-1 beta) and endotoxin (LPS). In contrast, mature offspring respond to physical stresses with an exaggerated activation of their hypothalamic-pituitary-adrenal (HPA) axis. The present work was aimed at determining if there was a differential influence of prenatal E exposure on the HPA axis responses to various stressors or if, alternatively, sexual maturation modified these responses. When administered IL-1 beta at 5 weeks age, E-treated intact male offspring released less ACTH, compared to control (C) or pair-fed (PF) animals. However, they showed an augmented response to LPS and a local inflammatory process induced by turpentine injection. At this same age, intact E females secreted significantly more ACTH in response to IL-1 beta, LPS and turpentine, than C or PF offspring. By 9 weeks of age, both E males and E females exhibited larger (p < .05) ACTH responses to all three immune stimuli. In order to determine whether sex steroids modulate the influence of E in females, ovariectomy was done prior to puberty. This treatment decreased the difference in the ACTH released by E and C rats in response to IL-1 beta, LPS and turpentine.These results show that while immature rats exposed to E prenatally released less ACTH in response to cytokines than C or PF animals did, this response was qualitatively reversed after puberty. At that time, the larger amounts of ACTH secreted by E offspring, compared to the other groups, were reminiscent of the hyperactive response of the HPA axis when these offspring were exposed to physical stress. Interestingly, removal of circulating ovarian steroids prevented the influence of E from being exerted. This suggests the presence of a functional relationship between the pathways influenced by prenatal E and those influenced by female sex steroids, that are important in regulating the activity of the HPA axis. Copyright (C) 1996 Elsevier Science Ltd.