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Circulating growth hormone binding protein levels and mononuclear cell growth hormone receptor expression in uremia. 2006

Joshua Greenstein, and Steven Guest, and Jane C Tan, and Padmaja Tummala, and Stefan Busque, and Ralph Rabkin
Department of Medicine, Stanford University, Stanford, CA, USA.

BACKGROUND Resistance to growth hormone (GH) in end-stage renal disease (ESRD) causes growth retardation and muscle wasting. In humans, circulating GH binding protein (GHBP), the extracellular domain of the GH receptor that is shed into the circulation and is believed to reflect tissue GH receptor levels, is reduced in uremia and suggests that cellular GH receptor levels are correspondingly reduced. If true, this could be a cause of GH resistance. We set out to establish whether serum GHBP levels reflect cellular GH receptor levels and whether changes in serum GHBP levels are related to nutritional or inflammatory status. METHODS GH receptor protein expression in peripheral blood mononuclear cells (PBMC) from 21 ESRD and 14 normal subjects were analyzed by fluorochrome flow cytometry. RESULTS The GH receptor density and percent total PBMCs expressing the GH receptor were similar in the 2 groups, and there was no difference in percent GH receptor positive T or B cells or monocytes. In contrast, serum GHBP levels were 80% lower in ESRD. GHBP levels did not correlate with serum albumin, body mass index, or muscle mass but seemed to be partly related to the log serum C-reactive protein levels. CONCLUSIONS Serum GHBP levels are markedly reduced in ESRD; this seems to occur independent of nutritional status and may in part be caused by inflammation. Because GH receptor expression on PBMC of ESRD and control subjects was similar, our findings argue against a reduction in GH receptor as a cause of GH resistance and the use of serum GHBP levels as a reliable marker of specific tissue GH receptor levels.

UI MeSH Term Description Entries
D007334 Insulin-Like Growth Factor I A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor. IGF-I,Somatomedin C,IGF-1,IGF-I-SmC,Insulin Like Growth Factor I,Insulin-Like Somatomedin Peptide I,Insulin Like Somatomedin Peptide I
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D007963 Leukocytes, Mononuclear Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules. Mononuclear Leukocyte,Mononuclear Leukocytes,PBMC Peripheral Blood Mononuclear Cells,Peripheral Blood Human Mononuclear Cells,Peripheral Blood Mononuclear Cell,Peripheral Blood Mononuclear Cells,Leukocyte, Mononuclear
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009752 Nutritional Status State of the body in relation to the consumption and utilization of nutrients. Nutrition Status,Status, Nutrition,Status, Nutritional
D011986 Receptors, Somatotropin Cell surface proteins that bind GROWTH HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells. Activation of growth hormone receptors regulates amino acid transport through cell membranes, RNA translation to protein, DNA transcription, and protein and amino acid catabolism in many cell types. Many of these effects are mediated indirectly through stimulation of the release of somatomedins. Growth Hormone Receptors,Receptors, Growth Hormone,Somatomammotropin Receptors,Somatotropin Receptors,Growth Hormone Receptor,Receptor, Growth Hormone,Receptors, Somatomammotropin,Somatomammotropin Receptor,Somatotropin Receptor,Hormone Receptor, Growth,Hormone Receptors, Growth
D002097 C-Reactive Protein A plasma protein that circulates in increased amounts during inflammation and after tissue damage. C-Reactive Protein measured by more sensitive methods often for coronary heart disease risk assessment is referred to as High Sensitivity C-Reactive Protein (hs-CRP). High Sensitivity C-Reactive Protein,hs-CRP,hsCRP,C Reactive Protein,High Sensitivity C Reactive Protein
D002469 Cell Separation Techniques for separating distinct populations of cells. Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell

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