A MATHEMATICAL-MODEL FOR APPRAISAL OF THE IMPACT OF GH BINDING-PROTEIN ON GH RECEPTOR-BINDING

Discrepancies between GH measurements and growth rate of children have complicated diagnosis in a variety of clinical conditions. The compet ition of GH-BP with the GH-receptor towards GH-receptor binding can ha ve a role in these discrepancies. A mathematical model was developed f or appraising the availability of GH for receptor binding from measure ments of serum GH by RIA and serum GH binding protein (BP) by a bindin g assay. Eighteen patients with high GH-BP (obesity), normal GH-BP (no rmal control) or low GH-BP (children, anorexia nervosa or cirrhosis of the liver) were the subjects of this study. Sera of patients,vith hig h, normal or low GH-BP levels were analyzed for their competition with I-125hGH binding to rabbit liver membranes. Serum GH was measured b y a commercial polyclonal RIA. Serum GH-BP was measured by a binding a ssay with dextran-coated charcoal separation. Receptor availability fo r GH was assessed by displacing of I-125hGH from rabbit liver membra nes. The decline in receptor availability for each hGH value, caused b y GH-BP competition with the receptor, was calculated by subtraction o f the percent displacement in the absence of GH-BP from the percent di splacement in the presence of a given GH-BP value. The results were an alyzed statistically to give a series of polynomes. These enabled the calculation of an activity factor for serum RTA GH levels, that should predict the receptor availability of each GH level, according to the concomitant GH-BP level. A trend analyses of the activity factors (AF) as a function of serum GH and GH-BP levels revealed a multipolynomial curvilinear regression, which enables the calculation of AF from thes e 2 measured parameters.