Decreased heat tolerance is associated with hypothalamo-pituitary-adrenocortical axis impairment

When rats are exposed to heat, they adapt themselves to the stressor with a wide inter-individual variability. Such differences in heat tolerance may be related to particularities in the hypothalamo-pituitary-adrenocortical (HPA) axis activation. To further this hypothesis, 80 rats instrumented with a telemetric device for abdominal temperature (Tabd) measurement were separated into two groups. Sixty-eight rats were exposed during 90 min at an ambient temperature of 40 degrees C, and 12 rats to an ambient temperature of 22 degrees C. Heat-exposed rats were then divided into three groups using the a posteriori k-means clustering method according to their Tabd level at the end of heat exposure. Heat tolerant rats (Tol, n=30) exhibiting the lowest Tabd showed a slight dehydration, a moderate triglyceride mobilization, but the highest plasma adrenocorticotropic-hormone (ACTH) and corticosterone levels. Conversely, heat exhausted rats (HE, n=14) presented the highest Tabd, a higher degree of dehydration, a greater metabolic imbalance with the lowest plasma triglyceride level and the highest lactate concentration, as well as a lowest plasma corticosterone and ACTH levels. The fact that the proopiomelanocortin (POMC) mRNA content within the pituitary was low despite of a high c-fos mRNA level is also relevant. Current inflammatory processes in HE rats were underlined by lower inhibitory factor kappaBalpha (IkappaBalpha) mRNA and higher tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mRNA. In conclusion, data show that intolerance to heat exposure is associated to an HPA axis impairment, possibly related to changes occurring in the IkappaBalpha and TNF-alpha mRNA levels.     

侧脑室注射6-OHDA对寒冷应激诱导的大鼠血浆ACTH含量的改变

目的　观察侧脑室注射 6 OHDA对 4℃寒冷应激诱导的血浆ACTH含量的改变。方法　成年Wistar雄性大鼠 3 0只 ,随机分成 5组 (n =6) ,分别为空白对照组、寒冷应激组、6 羟基多巴胺 (6 OHDA)非应激组、6 OHDA +寒冷应激组、配药液 +寒冷应激组。所有动物处理后立即取静脉血用放射免疫法测定其血浆ACTH含量。结果　 4℃寒冷应激 4h后血浆ACTH含量明显升高 ,与正常对照组相比有明显差异 (P <0 .0 1) :6 OHDA侧脑室注射后再寒冷应激 ,血浆ACTH含量不再明显升高。结论　寒冷应激可能通过脑内儿茶酚胺能系统调控HPA轴的活性     

外源性褪黑素对慢性应激抑郁模型大鼠行为学及血清相关激素含量的影响

目的通过观察不同剂量的外源性褪黑素对慢性应激抑郁模型大鼠行为学及血清中5-HT、CRH、ACTH、CORT含量的影响,探讨外源性褪黑素对抑郁症的治疗作用。方法 48只SD大鼠随机分为4组:空白对照组、模型对照组、褪黑素高剂量组、褪黑素低剂量组,每组12只。采用慢性轻度不可预见性应激和孤养方法复制慢性应激抑郁模型,灌胃给予治疗组不同剂量(5.0、10.0 mg·kg-1)的褪黑素加以干预,以体重、糖水试验、旷野试验观察实验前后大鼠行为学的改变。应用酶联免疫吸附法对大鼠血清中5-HT、CRH、ACTH、CORT的含量进行检测。结果从第7天开始,模型组、褪黑素低量组、褪黑素高剂量组的体重增长趋势开始降低,从第14天开始,模型对照组大鼠体重有下降趋势;从第14天开始褪黑素低剂量组、褪黑素高剂量组的糖水摄入量增长趋势降低,模型对照组的糖水摄入量呈下降趋势;第21天,与模型对照组相比,褪黑素低剂量和褪黑素高剂量组大鼠的水平和垂直运动次数都有显著性增多。与空白对照组相比,模型对照组血清5-HT的含量降低、血清CRH、ACTH、CORT含量升高,与模型对照组相比,褪黑素低剂量组和褪黑素高剂量组的血清5-HT含量均显著升高,血清CRH、CORT、ACTH含量均显著降低。结论外源性褪黑素对慢性应激抑郁模型大鼠抑郁行为有改善作用,也可以提高慢性应激抑郁模型大鼠血清中5-HT的含量,降低慢性应激抑郁模型大鼠血清中CRH、ACTH、CORT的含量,但它们之间的具体量效关系有待进一步研究。     

The role of protein synthesis in adrenocorticotrophin action: Effects of cycloheximide and puromycin on the steroidogenic response of isolated adrenocortical cells

The kinetics of the corticosteroidogenic response to adrenocorticotrophin (ACTH) have been investigated using collagenase dispersed adrenocortical cells. Following the addition of ACTH at a concentration that was maximal for steroidogenesis, there was a time-lag of about 3 min before increased steroidogenesis became apparent. This lag was extended (about two-fold) in the presence of a half-maximal concentration of ACTH. Preincubation of cells with submaximal concentrations of both cycloheximide and puromycin extended the time-lag observed following ACTH addition. Increasing doses of cycloheximide or puromycin concomitantly inhibited protein synthesis and steroidogenesis. Moreover cycloheximide, at a dose that halved protein synthesis, also inhibited steroidogenesis by 54–61% for a range of ACTH concentrations (1 × 10⁻⁴ to 1 × 10⁻² I.U./ml).It is concluded that the delay before ACTH-stimulated steroidogenesis is not attributable solely to the time taken for ribosomes to read of from the mRNA strand, the code for protein regulator(s). The results are discussed in terms of steroidogenic mechanisms whereby ACTH either induces de novo protein synthesis or activates a pre-existing, but labile, protein. In this latter scheme the steroidogenic rate observed under various conditions would be directly dependent upon the intracellular level of such an activated protein regulator. The half-life of labile protein, implicated as regulating steroidogenesis, was estimated at 2–4 min in this adrenal cell suspension system.     

异位ACTH综合征患者糖代谢异常的特点分析

通过对经病理证实的117例库欣综合征患者临床资料的分析,探讨异位ACTH综合征(EAS)糖代谢异常的特点.117例患者分为3组:EAS组9例,库欣病组(CD)67例,肾上腺皮质腺瘤组(AA)41例.与CD组和AA组相比,EAS组继发性糖尿病发生率高,血糖水平高,HbAlc水平低,原发病灶根治术后,血糖降至正常.     

Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal responses to chronic cold stress in rats

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.