Effect of human growth hormone (GH)-binding protein in human serum on GH binding to rabbit liver membranes.
The sequence identity of growth hormone-binding protein (GH-BP) with the extracellular domain of GH receptors raised the possibility that circulating GH-BP might affect the binding of human GH (hGH) to its receptors, and thus, its biological effects. To test this hypothesis, we tested the effects of sera with low GH-BP levels (obtained from prepubertal children, girls with anorexia nervosa [AN], and patients with hepatic cirrhosis), normal control sera, and sera with high GH-BP levels (obtained from obese patients) on hGH binding to its receptors. GH-BP activity in patients' sera was measured by incubation with [125I]hGH and the separation of bound hGH from free hGH with dextran-coated charcoal. The effect of GH-BP was studied by preincubation of patients' sera with increasing concentrations of hGH, followed by incubation with [125I]hGH and a rabbit liver membrane preparation known to be rich in GH receptors, and finally by measuring hGH bound to the receptors. In this study, we report on the ability of GH-BP to reduce the inhibitory capacity (IC50) of hGH on [125I]hGH binding to GH receptors. The concentration of GH-BP in serum is positively correlated with the IC50 of hGH incubated with different sera on [125I]hGH binding to its receptors (n = 21; r = .886, P less than .001). In the presence of high serum GH-BP levels, such as those observed in obesity (20.13% +/- 0.71%/0.05 mL serum), the IC50 values were significantly higher than those obtained with sera containing GH-BP levels lower than those measured in human control subjects, such as from prepubertal children, AN patients, and cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Amit
T
T
Rappaport Family Research Institute, Technion, Haifa, Israel.
Barkey
R J
RJ
Youdim
M B
MB
Hochberg
Z
Z
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000097:blood / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D011817:Rabbits; D011986:Receptors, Somatotropin / Q000502:physiology
D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D013006:Growth Hormone; C051815:somatotropin-binding protein