The Clinical Significance of Growth Hormone Binding Protein

Abstract

Abstract. The clinical significance of Growth Hormone Binding Protein (GHBP) is seen in at least three distinct, yet interrelated ways. First, GHBP serves as a serum marker for the GH-receptor level: it is absent in most patients with GH-receptor deficient Laron type dwarfism; it is low in liver cirrhosis, hypothyroidism and malnutrition, where GH-receptor insufficiency has been shown; it is high in hyperthyroidism and obesity, where GH-receptor is increased: and it increases with GH therapy, as reported for rat GH-receptor. Secondly, GHBP slows serum GH clearance and, hence, sustains higher GH levels; serum GHBP correlates negatively with GH disappearance rate, and was suggested as a pharmacological enhancer of GH activity. Finally, GHBP competes with the GH-R on GH binding, and interferes with GH biological activity: in vitro GHBP decreases GH activity, in the rat increasing levels of GHBP result in GH resistance, and in human serum, increasing levels of GHBP diminish GH bioactivity, as measured in vitro by the potency to displace hGH from GH-receptor. We suggest an algorithm to correct RIA-GH levels for the interference effect of GHPB on its biological activity. Our study of normal short children and GHD disclosed negative correlation with serum GH and higher levels in girls then in boys. GHBP did not predict growth response to hGH therapy. It is concluded that the significance of GHBP and its impact on GH bioavailibility and activity is complex, and involves consideration of the GH-receptors, GH volume distribution, GH clearance and competition with the GH-receptors. [51]. The amino acid sequence of the rabbit GH-BP has been shown to be identical with the extracellular domain of the GHreceptor [6].The mechanism of GH-BP synthesis and secretion is not fully understood.