Plasma somatomedin-binding proteins in hypopituitarism: changes during growth hormone therapy

The somatomedin (SM) peptides are carried in plasma complexed to specific SM-binding proteins (SMBPs). In addition to the SMBP in the complex, there is an unsaturated SMBP in plasma in which the SMBP is not occupied by SMs. We have compared levels of unsaturated SMBP in 7 normal adults to those in 21 children with GH deficiency before and during treatment with hGH (0.1 U/kg.day) for 4 days. In addition, the SM-C/insulin-like growth factor I (IGF-I) content of each plasma was measured by RIA. There was a significant (P less than 0.01) difference in unsaturated SMBP levels between normal controls (17.8 +/- 0.8% bound/20 microliters) and untreated hypopituitary patients (27.8 +/- 2.2% bound/20 microliters). Thus, a lower SM-C/IGF-I content was associated with a higher unsaturated SMBP level. Furthermore, there was a significant negative correlation between SM-C/IGF-I content and unsaturated SMBP in untreated hypopituitary patients (r = 0.73; P less than 0.0001). Treatment with hGH normalized the mean unsaturated SMBP level in hypopituitary patients within 2 days. Full displacement curves and Scatchard analysis showed that the increased unsaturated SMBP level in hypopituitary plasma was entirely due to an increased affinity (8.4 X 0.9 X 10(-10) M) compared to normal (2.3 X 0.2 X 10(-9) M). A higher affinity form of unsaturated SMBP is uniquely present in hypopituitarism and disappears with hGH treatment. The measurement of this unsaturated SMBP mirrors the SM peptide content.