No evidence for a defect in growth hormone binding to liver membranes in thalassemia major.
To test the hypothesis of a defect in GH-receptor interaction, which could explain the growth failure of thalassemic children, the binding of [125I]human (h) GH to membrane fractions prepared from liver biopsies was studied. Small amounts of liver were obtained from 6 girls and 11 boys with homozygous beta-thalassemia, aged 3-15 yr, all prepubertal, at the time of splenectomy. Specific binding of [125I]hGH ranged from 0.37-5.11% of the added radioactivity/100 micrograms liver membrane protein, with variations in both receptor number and binding affinity. This 14-fold variation in hGH binding to liver membranes of thalassemic children was comparable to that in membrane fractions of livers obtained from normal donors at the time of liver transplant. The binding of insulin to liver membranes from the thalassemic patients ranged from 9.8-17.9% of the added radioactivity/100 micrograms membrane protein and from 2.8-15.0%/100 micrograms membrane protein in the normal donors. Insulin and GH binding to liver membranes did not vary in a consistent way. A 3-fold difference was found in 5'-nucleotidase activity of the membrane fractions. Histological hepatic modifications were assessed with respect to siderosis and fibrosis. No correlation was found between these parameters and GH binding. These results suggest that possible membrane alterations are not the only reason for the variations in hGH binding. All patients had retarded growth, and all but 2 had low plasma insulin-like growth factor I levels. No relationship was found between the level of GH binding to liver membranes and the growth failure. Thus, a defect in GH binding to liver membranes is probably not the cause of the growth retardation of thalassemic children.
Postel-Vinay
M C
MC
Unité de Recherches en Biologie et Pathologie de la Croissance, Hôpital des Enfants-Malades, Paris, France.
Girot
R
R
Leger
J
J
Hocquette
J F
JF
McKelvie
P
P
Amar-Costesec
A
A
Rappaport
R
R
D000293:Adolescent; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D004393:Dwarfism, Pituitary / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011986:Receptors, Somatotropin / Q000187:drug effects / Q000378:metabolism*; D013789:Thalassemia / Q000378:metabolism*
D007328:Insulin; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone