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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BPC-H (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
Zip Code
Hölttä, Mikko; Dean, Robert A; Siemers, Eric et al. (2016) A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans. Alzheimers Res Ther 8:11
Mertins, Philipp; Mani, D R; Ruggles, Kelly V et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534:55-62
Karner, Courtney M; Esen, Emel; Chen, Jiakun et al. (2016) Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation. J Biol Chem 291:13028-39
Murata, Takahiro; Dietrich, Hans H; Horiuchi, Tetsuyoshi et al. (2016) Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles. Neurosci Res 107:57-62
Sterl, Karin; Wang, Songyan; Oestricker, Lauren et al. (2016) Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides 82:76-84
Lucey, Brendan P; Mawuenyega, Kwasi G; Patterson, Bruce W et al. (2016) Associations Between β-Amyloid Kinetics and the β-Amyloid Diurnal Pattern in the Central Nervous System. JAMA Neurol :
Wang, Xiaojing; Wu, Yunkou; Soesbe, Todd C et al. (2015) A pH-Responsive MRI Agent that Can Be Activated Beyond the Tissue Magnetization Transfer Window. Angew Chem Int Ed Engl 54:8662-4
Kovacs, Erika; Das, Rahul; Wang, Qi et al. (2015) Analysis of the Role of the C-Terminal Tail in the Regulation of the Epidermal Growth Factor Receptor. Mol Cell Biol 35:3083-102
Frank, Pinar; Siebenhofer, Bernhard; Hanzer, Theresa et al. (2015) Proteo-lipobeads for the oriented encapsulation of membrane proteins. Soft Matter 11:2906-8
Thimgan, Matthew S; Seugnet, Laurent; Turk, John et al. (2015) Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila. Sleep 38:801-14

Showing the most recent 10 out of 666 publications