Stimulation of the 150-kilodalton insulin-like growth factor-binding protein-3 ternary complex by continuous and pulsatile patterns of growth hormone(GH) administration in GH-deficient patients

In the circulation insulin-like growth factor I(IGF-I), IGF-binding protein 3 (IGFBP-3), and the acid-labile subunit (ALS) form a 150-kDa ternary comp lex that is of importance for the regulation of IGF-I bioactivity. GH admin istration is known to increase each of the single components of the ternary complex, and in GH-deficient rats formation of the 150-kDa complex is indu ced more by continuous than by pulsatile GH patterns. The aim of the presen t studies was to study the effects of the GH administration pattern on the formation of the 150-kDa ternary complex in humans. A fixed total GH dose ( 2 IU/ m(2).24 h) was administered iv randomly as 1) continuous infusion or 2) eight bolus injections to five GH-deficient patients over a period of 24 h. GH administration significantly increased serum IGF-I and IGFBP-3 level s and the IGF-I/IGFBP-3 ratio. IGF-I levels increased most pronouncedly aft er continuous administration (P < 0.01). Serum ALS levels increased signifi cantly (both P < 0.005) from 94 +/- 21 to 180 +/- 29 (infusion) and from 85 +/- 17 to 155 +/- 17 nmol/L (pulses). Employment of neutral size exclusion chromatography enabled separation of IGFBP-3 in ternary complex and noncom plex-bound fractions. IGFBP-3 in the ternary complex increased significantl y after GH administration [by 44% (P = 0.048) during infusion and by 62% (P = 0.004) during bolus]. The noncomplex-associated IGFBP-3 fraction, howeve r, did not increase significantly after GH administration (P = NS). Finally , formation of the ternary complex was unaffected by the pattern of GH deli very. In conclusion, short-term GH administration increased all components of the 150-kDa ternary complex. Higher levels of IGF-I after constant GH ex posure could indicate an increased bound fraction. However, the GH pattern did not influence the induction of the ternary complex itself. Continuous a nd intermittent GH patterns may be clinically equally effective during long term GH therapy, as judged by levels of the components of the ternary compl ex.