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.
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