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A mathematical model for appraisal of the impact of GH binding protein on GH receptor binding
Z Hochberg1, M B Youdim, T Amit
1Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Insights
Growth hormone (GH) measurements can be misleading due to GH-binding protein (GH-BP) competition. A new model predicts GH receptor availability, improving diagnostic accuracy for growth disorders.
Area of Science:
- Endocrinology
- Biochemistry
- Mathematical Biology
Background:
- Discrepancies between serum growth hormone (GH) levels and a child's growth rate present diagnostic challenges.
- Growth hormone-binding protein (GH-BP) competition with the GH receptor may explain these measurement discrepancies.
Purpose of the Study:
- To develop a mathematical model for assessing GH availability for receptor binding.
- To correlate serum GH and GH-BP levels with GH receptor availability.
Main Methods:
- Developed a mathematical model using serum GH (RIA) and GH-BP (binding assay) measurements.
- Analyzed serum samples from 18 patients with varying GH-BP levels (high, normal, low).
- Assessed GH receptor availability by measuring [125I]hGH displacement from rabbit liver membranes.
Main Results:
- Quantified the reduction in receptor availability due to GH-BP competition.
- Developed statistical polynomial equations to predict receptor availability based on GH and GH-BP levels.
- Introduced an 'activity factor' to adjust serum GH measurements for GH-BP interference.
Conclusions:
- The developed mathematical model and activity factor can predict GH receptor availability.
- This approach aids in interpreting GH measurements more accurately, especially in conditions with altered GH-BP levels.
Abstract:
Discrepancies between GH measurements and growth rate of children have complicated diagnosis in a variety of clinical conditions. The competition of GH-BP with the GH-receptor towards GH-receptor binding can have a role in these discrepancies. A mathematical model was developed for appraising the availability of GH for receptor binding from measurements of serum GH by RIA and serum GH binding protein (BP) by a binding assay. Eighteen patients with high GH-BP (obesity), normal GH-BP (normal control) or low GH-BP (children, anorexia nervosa or cirrhosis of the liver) were the subjects of this study. Sera of patients with high, normal or low GH-BP levels were analyzed for their competition with [125I]hGH binding to rabbit liver membranes. Serum GH was measured by a commercial polyclonal RIA. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Receptor availability for GH was assessed by displacing of [125I]hGH from rabbit liver membranes. The decline in receptor availability for each hGH value, caused by GH-BP competition with the receptor, was calculated by subtraction of the percent displacement in the absence of GH-BP from the percent displacement in the presence of a given GH-BP value. The results were analyzed statistically to give a series of polynomes. These enabled the calculation of an activity factor for serum RIA GH levels, that should predict the receptor availability of each GH level, according to the concomitant GH-BP level.(ABSTRACT TRUNCATED AT 250 WORDS)