Expression of growth hormone receptor by peripheral blood lymphocytes in children: evaluation in clinical conditions of impaired growth.
OBJECTIVE
It is widely accepted that the haematopoietic system is a target of growth hormone action and that GH may act as a lymphokine. The expression of GH receptors (GHR) on human peripheral blood lymphocytes (PBL) has been reported previously in adult donors by dual fluorochrome flow cytometry. The aim of this study was to apply the cytofluorimetric method to the analysis of GHR expression on PBL in various human conditions characterized by different patterns of growth due to age or physiopathological conditions.


METHODS
PBL from 38 normal (control) subjects (7 newborns, 18 prepubertal children, 13 adults) were studied in order to provide age-related physiological data. Twenty-two short children (18 with idiopathic short stature, 4 with Ullrich-Turner syndrome) were studied to determine the expression of GHR in conditions of impaired longitudinal growth which may or may not require GH treatment.


METHODS
Analysis was performed using a fluorescein isothiocyanate (FITC)-conjugated antibody specific for the GHR (mAb263) and phycoerythrin (PE)-anti CD2 (T and natural killer cells) or PE-anti CD2 (B cells) in dual fluorochrome flow cytometric assays. Results were expressed as mean fluorescent intensity (MFI).


RESULTS
Adult CD2+ coils exhibited a significantly higher GHR expression (MFI 347 +/- 40) than that expressed in children and newborns (MFI 285 +/- 36 and 299 +/- 41, respectively, P < 0.001). A significantly increased expression of GHR on CD2+ cells was also found in short children (MFI 330 +/- 42 vs 285 42- 36, respectively; P < 0.002), whereas Ullrich-Turner syndrome patients did not show any difference from their age and gender matched controls (254 +/- 52 and 288 +/- 40, respectively). A negative relationship was found between GHR expression on CD2+ cells and height-SDS (r - 0.54, P < 0.0001) or BMI (r - 0.4, P < 0.015) in controls and short children, independent of their GH secretory status. Expression of GHR and CD20+ cells was higher than that expressed on CD2+ cells in all subjects. No appreciable differences were found in the MFI levels of GHR expression on CD20+ cells either among the different age group controls or between short children or Ullrich-Turner syndrome patients. A significant downregulation of expression was shown in CD20+ (P < 0.008) but not CD2+ cells after 6 months of GH treatment in 6 short children who had a poor response to GH provocative tests.


CONCLUSIONS
GH receptor expression on immune cells in non-syndromic short children appears to be inversely related to the linear growth expression and BMI of the subjects, contrary to findings with hepatic derived serum GHBP. This finding may reflect alternate exon usage in lymphoid cells, and indicates that GH has a distinctive role in the immune system.
Valerio
G
G
Department of Pediatrics (DPMSC), University of Udine, School of Medicine, Italy.
Bond
H M
HM
Badolato
R
R
Petrella
A
A
Di Maio
S
S
Salerno
M
M
Waters
M J
MJ
Venuta
S
S
Tenore
A
A
D000328:Adult; D000375:Aging / Q000276:immunology; D018951:Antigens, CD20; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015992:Body Mass Index; D018801:CD2 Antigens; D002648:Child; D005260:Female; D005434:Flow Cytometry; D006128:Growth / Q000276:immunology; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011986:Receptors, Somatotropin / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018951:Antigens, CD20; D018801:CD2 Antigens; D011986:Receptors, Somatotropin; D013006:Growth Hormone