Circulating growth hormone binding protein levels and mononuclear cell growth hormone receptor expression in uremia.
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.
Department of Medicine, Stanford University, Stanford, CA, USA.
Joshua
J
Greenstein
Steven
S
Guest
Jane C
JC
Tan
Padmaja
P
Tummala
Stefan
S
Busque
Ralph
R
Rabkin
D000328:Adult; D000368:Aged; D000886:Anthropometry; D001402:B-Lymphocytes / Q000737:chemistry; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000097:blood*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D011986:Receptors, Somatotropin / Q000097:blood*; D012709:Serum Albumin / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry
D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D012709:Serum Albumin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein