CORTISOL AND THE GLUCOCORTICOID RECEPTOR IN MALNUTRITION AND ACUTE INFECTION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。仅严重的营养不良就被认为会导致高皮质醇血症。皮质醇的作用是通过糖皮质激素受体介导的，糖皮质激素受体在细胞质中结合激素，易位到细胞核并促进基因转录。这项观察性研究在患有和不患有急性感染的消瘦儿童中验证了消瘦与高皮质醇血症、糖皮质激素受体减少和受体向核易位减少有关的假设。28名马拉维儿童参加；消瘦合并感染14例，消瘦无感染6例，营养良好伴感染8例。入院时测定游离血清皮质醇、IL-6、TNF-a、全身蛋白水解产生的亮氨酸、全细胞和核白细胞糖皮质激素受体的含量。消瘦症和营养良好的消瘦症患儿感染后血清游离皮质醇浓度较未感染消瘦症患儿升高（14.0 ~ 6.9、24.6 ~ 19.8、5.8 ~ 2.9 μ g/L，平均SD， P < 0.05）。全细胞白细胞糖皮质激素受体的数量在所有儿童中相似（0.48 ~ 0.33信号单位），但在感染的麻风患儿中细胞核中的数量最多，其次是未感染的麻风患儿，然后是营养良好的感染儿童（0.54 ~ 0.58,0.19 ~ 0.13,0.02 ~ 0.5信号单位，平均SD， P < 0.05，所有比较均采用方差分析）。这些发现表明，高皮质醇血症并不仅仅与营养不良有关，而是与急性感染有关。糖尿病患者核糖皮质激素受体丰度的增加表明，除了循环糖皮质激素浓度外，营养状况还通过其他机制调节糖皮质激素受体的作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Severe malnutrition alone is believed to cause hypercortisolemia. Cortisol's effects are mediated through the glucorticoid receptor, which binds the hormone in the cytosol, translocates to the nucleus and promotes gene transcription. This observational study in marasmic children with and without acute infection tested the hypothesis that marasmus is associated with hypercortisolemia, less glucocorticoid receptor and less receptor translocation to the nucleus. 28 Malawian children participated; 14 with marasmus and infection, 6 with marasmus without infection and 8 well-nourished with infection. Free serum cortisol, IL-6 and TNF-a, leucine derived from whole-body proteolysis and the amount of whole-cell and nuclear leucocyte glucocorticoid receptor were measured upon admission. Free serum cortisol concentration was increased in marasmic and well-nourished children with infection compared to uninfected children with marasmus (14.0 ¿ 6.9, 24.6 ¿ 19.8, 5.8 ¿ 2.9 micro g/L, mean ¿ SD, P < 0.05). The amount of whole-cell leucocyte glucorticoid receptor was similar in all children (0.48 ¿ 0.33 signal units), but the amount in the nucleus was greatest in marasmic children with infection, followed by uninfected marasmic children and then well-nourished, infected children (0.54 ¿ 0.58, 0.19 ¿ 0.13, 0.02 ¿ 0.5 signal units, mean ¿ SD, P < 0.05 for all comparisons by ANOVA). These findings suggest that hypercortisolemia is not associated with malnutrition alone, but does occur appropriately with acute infection. The increased nuclear glucocorticoid receptor abundance in marasmus demonstrates that nutritional status modulates glucocorticoid receptor action by mechanisms in addition to circulating glucocorticoid concentrations.