Kim C K, Giberson P K, Yu W, Zoeller R T, Weinberg J
Department of Anatomy, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Alcohol Clin Exp Res. 1999 Feb;23(2):301-10.
Animals prenatally exposed to ethanol typically exhibit hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors. In contrast to previous studies that have investigated effects of prenatal ethanol exposure on HPA responses to acute or intermittent stressors, our study investigated HPA responses to a chronic continuous stressor, cold stress (4 degrees C for 0, 1, or 3 days). We tested the hypothesis that prenatal ethanol exposure would result in increased plasma corticosterone (CORT) and adrenocorticotropin (ACTH) responses and increased peptide [corticotropin-releasing factor and vasopressin] mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus compared to that in control animals. In addition, CORT and ACTH responses were measured after exposure to an acute stressor (i.p. isotonic saline injection), superimposed during chronic cold exposure, to examine possible sensitization of the HPA response to the acute stress. Thus, blood samples were collected at the end of each of the three periods of cold exposure, either before (0 min) or 15 min after acute stress. The subjects were adult male and female Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment groups. Exposure to cold stress resulted in significant body weight loss in E males at 1 day and in both males and females of all prenatal treatment groups by 3 days of cold stress. Males in all prenatal groups also exhibited significant increases in adrenal weight:body weight ratios. Cold stress alone (0 min condition) increased CORT levels in E males and overall ACTH levels in E males and females compared to controls. ACTH levels were also higher overall in E compared to control males after acute stress (15 min condition). Sensitization of the CORT response to acute stress was observed in males but not females across all prenatal treatment groups. Corticotropin-releasing factor and vasopressin mRNA levels in the PVN were not significantly affected by prenatal treatment or chronic cold stress in either males or females. In contrast, both males and females displayed increases in PVN thyrotropin-releasing hormone (TRH) mRNA levels after cold stress. These data support and extend previous work demonstrating differential effects of prenatal ethanol exposure on HPA responsiveness of male and female offspring, and suggest that E males may be more vulnerable to the effects of chronic cold stress than E females.
产前暴露于乙醇的动物通常表现出下丘脑 - 垂体 - 肾上腺（HPA）对应激源的反应过度。与之前研究产前乙醇暴露对HPA对急性或间歇性应激源反应的影响不同，我们的研究调查了HPA对慢性持续性应激源——冷应激（4摄氏度，持续0、1或3天）的反应。我们检验了这样一个假设：与对照动物相比，产前乙醇暴露会导致血浆皮质酮（CORT）和促肾上腺皮质激素（ACTH）反应增加，以及下丘脑室旁核（PVN）中肽类[促肾上腺皮质激素释放因子和血管加压素]mRNA水平升高。此外，在慢性冷暴露期间叠加急性应激源（腹腔注射等渗盐水）后，测量CORT和ACTH反应，以检查HPA对急性应激反应的可能致敏作用。因此，在冷暴露的三个阶段结束时，即在急性应激前（0分钟）或急性应激后15分钟采集血样。实验对象是来自产前乙醇（E）、配对喂养（PF）和自由摄食对照（C）处理组的成年雄性和雌性Sprague-Dawley大鼠后代。冷应激导致E组雄性大鼠在1天时体重显著减轻，所有产前处理组的雄性和雌性大鼠在冷应激3天时体重均显著减轻。所有产前组的雄性大鼠肾上腺重量与体重之比也显著增加。单独冷应激（0分钟情况）使E组雄性大鼠的CORT水平升高，E组雄性和雌性大鼠的总体ACTH水平高于对照组。急性应激后（15分钟情况），E组雄性大鼠的总体ACTH水平也高于对照雄性大鼠。在所有产前处理组的雄性大鼠中观察到CORT对急性应激的致敏作用，而雌性大鼠未观察到。PVN中促肾上腺皮质激素释放因子和血管加压素的mRNA水平在雄性或雌性大鼠中均未受到产前处理或慢性冷应激的显著影响。相反，冷应激后雄性和雌性大鼠PVN中促甲状腺激素释放激素（TRH）的mRNA水平均升高。这些数据支持并扩展了先前的研究工作，证明产前乙醇暴露对雄性和雌性后代HPA反应性有不同影响，并表明E组雄性大鼠可能比E组雌性大鼠更容易受到慢性冷应激的影响。
