Regulation of plasma growth hormone-binding proteins in health and disease

Abstract

Binding proteins (BP) for growth hormone (GH) have recently been discovered in human plasma. The main BP is related to the GH receptor and probably corresponds to the extracellular portion of the receptor. The BP influence several aspects of GH homeostasis and action. Their level and activity in blood, therefore, become important variables in overall GH physiology. However, to date little is known about the regulation of GH-BP in health and disease. To gain initial information about this point, GH-BP activity was examined in the plasma of 124 subjects with various physiologic and pathologic conditions. The conditions were selected to provide basic physiologic data (men, women, children, age, pregnancy) and to investigate key disease states attended by abnormal GH physiology (liver cirrhosis, uremia, infection, acromegaly). A standardized GH binding assay was used to measure BP activity as an index of BP levels. Both the principal, high affinity BP (peak II) and the minor, low affinity BP (peak I) showed considerable individual variation in all groups. Neonates had the lowest levels of both BPs, but by the age of 1 year the levels had increased and remained fairly stable through the seventh decade. In males but not females between the ages of 1 and 20 years, the main (peak II) BP showed a slight upward trend, whereas the minor (peak I) BP declined moderately. Patients with cirrhosis showed the most variation in both BP, and uremic patients demonstrated decreased peak II, but not peak I, binding. Neither BP was affected in acromogaly. We conclude that BP activity in plasma is well conserved in most conditions, but substantial individual variability exists. BP activity increases dramatically during the first year of life. The two BPs appear to be differently regulated, with peak I, but not peak II, showing evidence for sex hormone dependence. The high affinity (peak II) BP carries 80% to 90% of the complexed GH. We propose to define one unit of BP activity as that contained in 1 mL of normal adult plasma. Under the conditions of analysis used in this report, one unit corresponds to a bound GH fraction of 30%.