Cortisol and its action on the glucocorticoid receptor in malnutrition and acute infection.
Severe malnutrition alone is believed to cause hypercortisolemia. Cortisol's effects are mediated through the glucocorticoid 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. Twenty-eight Malawian children participated; 14 with marasmus and infection, 6 with marasmus without infection, and 8 well nourished with infection. Free serum cortisol, interleukin 6 and tumor necrosis factor alpha, leucine derived from whole-body proteolysis, and the amount of whole-cell and nuclear leukocyte glucocorticoid receptor were measured upon admission. Free serum cortisol concentration was increased in marasmic and well-nourished children with infection compared with uninfected children with marasmus (14.2 [8.5, 16.3], 24.4 [15.0, 39.2], 5.1 [3.5, 7.0] microg/L, median [25th, 75th percentiles]; P < .05 by Kruskal-Wallis test). The amount of whole-cell leukocyte glucocorticoid 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 the amount in uninfected marasmic children, and then in well-nourished infected children (0.54 +/- 0.58, 0.19 +/- 0.13, 0.02 +/- 0.5 signal units [mean +/- SD]; P < .05 for all comparisons by analysis of variance). 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.
Manary
Mark J
MJ
Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. manary@kids.wustl.edu
Muglia
Louis J
LJ
Vogt
Sherri K
SK
Yarasheski
Kevin E
KE
D000208:Acute Disease; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism; D002675:Child, Preschool; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007223:Infant; D007962:Leukocytes / Q000378:metabolism; D008288:Malaria / Q000097:blood* / Q000150:complications; D011014:Pneumonia / Q000097:blood* / Q000150:complications; D011502:Protein-Energy Malnutrition / Q000097:blood* / Q000150:complications; D011965:Receptors, Glucocorticoid / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000150:complications
D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone