CIRCULATING LEVELS AND MOLECULAR-DISTRIBUTION OF THE ACID-LABILE (ALPHA) SUBUNIT OF THE HIGH-MOLECULAR-WEIGHT INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN COMPLEX

A RIA is described for the acid-labile (α) subunit of the high mol wt insulin-like growth factor (IGF)-binding protein complex, a glycoprotein of approximately 85, 000 daltons (˜85K) which combines with the GH-dependent binding protein (BP-53 or IGFBP-3) and IGF-I or IGF-II to form the complex. The assay shows relative specificity for higher primate species. Whereas amniotic fluid, cerebrospinal fluid, and seminal plasma contain virtually no immunoreactive a-subunit, the protein is easily detectable in 0.5-μL serum samples. Serum α-subunit levels are markedly age dependent, rising over 5-fold from birth to puberty, then remaining relatively constant throughout adulthood. In 170 children, there was a strong association between α-subunit and IGFBP-3 levels. Mean α-subunit levels (±sd) in adults were 24.2 ± 4.7 mg/L in 93 normal subjects, 54.1 ± 15.5 mg/L in 12 acromegalics, 6.5 ± 4.8 mg/L in 10 GH-deficient subjects, and 31.5 ± 5.7 mg/L in 18 third term pregnant women. In serum fractionated by gel chromatography, α-subunit appeared as a broad 100–150K peak. After depleting serum samples of IGFBP-3 by immunoaffinity chromatography, approximately one third of α-subunit remained, in a peak of about 100K, suggesting that two thirds of the total α-subunit in serum is present in the approximately 150K complex, and one third is uncomplexed. Development of this RIA for α-subunit will allow further study of regulation of the GH-dependent complex. © 1990 by The Endocrine Society.