Serum concentrations of growth hormone (GH) binding protein in GH-deficient patients: Impact of mode of GH administration

GH binding protein (GHBP) levels are influenced by the pattern of GH administration in rodents. The present four studies in GH-deficient (GHD) patients aim to determine serum GHBP concentrations during acute and longer-term continuous and intermittent patterns of GH delivery. In a randomized study, 10 patients received intravenous (i.v.) GH (2 IU/m(2)) for 24 h as: (1) a continuous infusion; (2) eight equal bolus injections; or (3) a combination of (1) and (2). In a second study, 10 patients were randomized to receive continuous i.v. and subcutaneous (s.c.) infusions of GH (0.033 mu g/kg/min) for 39 h. In a third study, 13 patients were randomized to receive GH (approximate to 3.15 IU) for 4 weeks in a cross-over design as (1) continuous s.c. infusion, or (2) daily s.c. injections. In study 4, eight patients were randomized to receive s.c. injections of GH (3 IU/m(2)) for 4 weeks each: (1) once daily (19:00 h); or (2) twice daily (19:00 h and 08:00 h) in a cross-over design. Serum GHBP was measured by a ligand mediated immunofunctional assay. Serum GHBP levels were not significantly different (P = 0.13) between the three modes of GH administration in study 1, but decreased slightly but significantly with time (P<0.001, by ANOVA) after all three treatments. Similarly, in study 2, effects on serum GHBP were not significantly different between continuous s.c. and i.v. infusion of GH. In study 3, GHBP concentrations were not significantly different after daily s.c. injections and continuous s.c. infusion of GH (P=0.84). Similar GHBP levels were also obtained in study 4 after once and twice daily GH injections (P=0.48). In conclusion, acute GH exposure (studies 1 and 2) in GH-deprived patients was associated with a slight decline in circulating GHBP levels. During more prolonged GH treatment, GHBP levels remain stable and independent of the pattern of circulating GH. These experimental data refute a temporal association between the circulating patterns of GH and GHBP. The previously reported differences in the metabolic effects of GH after constant and intermittent GH administration to GHD patients seem to be achieved independently of changes in GHBP concentrations.