ANALYSIS OF 24-HOUR PLASMA PROFILES OF GROWTH-HORMONE (GH)-BINDING PROTEIN, GH GH-BINDING PROTEIN-COMPLEX, AND GH IN HEALTHY-CHILDREN

Human blood contains a high affinity GH binding protein (GHBP) which c orresponds to the extracellular domain of the GH-receptor. It has been suggested that GHBP can modify the biological actions of GH, and alte r the distribution of GH in the body. To study the hormonal regulation of growth, it is therefore necessary to measure GHBP as well as GH. W e recently developed a ligand-mediated immunofunctional assay (LIFA) w hich allows separate quantitation of total GHBP (free and GH-bound) an d the complex formed by GH and GHBP (GH/GHBP-complex) in human blood. We have now used the ligand-mediated immunofunctional assay to measure GHBP levels in plasma profiles from healthy children. GH was measured by immunoradiometric assay. Fifteen 24-h plasma profiles from 12 heal thy children (3 girls and 9 boys) of different ages (6-15 yr), heights (-2.5 to +3.0 SD scores) and pubertal stages (1-4) were examined. Blo od was withdrawn continuously for 24 h and collected in 20-min fractio ns. Time series for GH, GHBP, and GH/GHBP-complex were analyzed by cro ss-correlation and Fourier analysis. GH was secreted in a pulsatile fa shion in all subjects. The concentration of the GH/GHBP-complex varied during the sampling period, and the changes correlated significantly with the GH pulses with correlation coefficients reaching maximum at z ero time lag. In contrast, the changes in the total GHBP concentration were minor (coefficients of variation approximately 10%), and not cor related to GH pulses. Fourier analysis showed similar spectral power p atterns for GH and GH/GHBP-complex, suggesting a diurnal rhythm (12- t o 24-h periods) as well as components of higher frequencies (around 4- h periods). Although there were only subtle fluctuations in the total GHBP concentration, Fourier transformation revealed a diurnal rhythm w ith nadir during the night, while components of higher frequencies wer e much less abundant. We conclude that variations in total GHBP as mea sured by LIFA during a 24-h sampling period are small and that the con centration can be estimated from a single random blood sample.