Decreased ternary complex formation and predominance of a 29 kDa IGFBP-3 fragment in human fetal serum.

Abstract

Insulin-like growth factor-I (IGF-I) has been proposed to be important in the endocrine control of fetal growth in humans, although serum IGF-I concentrations are 10-fold lower than during rapid pubertal growth. However, the bioavailability of IGF-I in fetal serum may be increased by changes in the specific IGF binding proteins (IGFBPs). We have recently suggested that the bioavailability of circulating IGF-I is increased in the human fetus due to the molar excess of IGF-I plus IGF-II relative to IGFBP-3 as well as the increased concentrations of IGFBP-2, which does not form a long-lived ternary complex. We have presently studied ternary complex formation between IGF, IGFBP-3, and acid labile subunit (ALS) to further assess if IGF-I bioavailability is increased in human fetal serum. In 19-35 week gestation fetal sera, a markedly decreased formation of the ternary complex was demonstrated by the general absence of IGFBP-3 (detected by Western immunoblotting) in the approximately 130-150 kDa ternary complex after neutral size chromatography. The predominant form of IGFBP-3 in fetal serum was a 29 kDa fragment, which, following deglycosylation by Endoglycosidase-F, was demonstrated to consist of a approximately 20 kDa protein core. Despite the predominance of the 29 kDa IGFBP-3 fragment, we have previously demonstrated that the IGFBP-3 protease activity is not increased in fetal serum, in contrast to pregnancy or non-insulin dependent diabetes mellitus (NIDDM) sera.(ABSTRACT TRUNCATED AT 250 WORDS)