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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR000954-29
Application #
7355174
Study Section
Special Emphasis Panel (ZRG1-BPC-H (40))
Project Start
2006-02-01
Project End
2007-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
29
Fiscal Year
2006
Total Cost
$5,897
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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