GROWTH HORMONE-BINDING PROTEIN-RELATED IMMUNOREACTIVITY IN THE SERUM OF PATIENTS WITH ACROMEGALY IS REGULATED INVERSELY BY GROWTH-HORMONE CONCENTRATION

In this report we describe a newly developed radioimmunoassay (RIA) fo r the determination of the high-affinity growth hormone-binding protei n (GHBP) in human blood. Using this RIA for the measurement of GHBP in serum of 29 patients with acromegaly, decreased concentrations were f ound compared to the normal range, depending on the activity of the di sease. Growth hormone-binding protein was correlated inversely to log GH (r = -0.7, p < 0.001). A weaker relationship was shown between the GHBP activity determined in a functional assay based on charcoal separ ation and log GH (r = -0.51, p < 0.01). While insulin-like growth fact or I (IGF-I) and IGF binding protein 3 (IGFBP-3) were correlated direc tly to log GH (r = 0.77 and r = 0.66, p < 0.001), an inverse and weake r relationship was evident between GHBP measured by RIA and IGF-I or I GFBP-3 (r = -0.61 and r = -0.57, p < 0.01). In contrast, no correlatio n could be detected between data of the functional GHBP assay and IGF- I or IGFBP-3. These results suggest, that: (1) in patients with acrome galy the GH receptor density in tissue reflected by the GHBP serum lev els seems to be down-regulated, depending on the increased GH level; ( 2) low GHBP concentrations indicate an active disease in acromegaly an d may be of diagnostic interest; (3) presuming that the GH receptor de nsity is related to GH sensitivity, the variation of GH sensitivity is less important for IGF-T and IGFBP-3 production than the circulating GH concentration, at least in the situation of acromegaly; (4) because endogenous GH does not interfere in that assay, the RIA provides a va luable tool for the investigation of regulations between GH, GHBP and the GH receptor, especially in patients with acromegaly. The GHBP leve ls may be used as a sensitive parameter of GH oversecretion and tissue sensitivity to this hormone.