Circulating Levels and Molecular Distribution of the Acid-Labile (α) Subunit of the High Molecular Weight Insulin-Like Growth Factor-Binding Protein Complex*

Abstract

A RIA is described for the acid-labile (alpha) subunit of the high mol wt insulin-like growth factor (IGF)-binding protein complex, a glycoprotein of approximately 85,000 daltons (approximately 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 alpha-subunit, the protein is easily detectable in 0.5-microL serum samples. Serum alpha-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 alpha-subunit and IGFBP-3 levels. Mean alpha-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, alpha-subunit appeared as a broad 100-150K peak. After depleting serum samples of IGFBP-3 by immunoaffinity chromatography, approximately one third of alpha-subunit remained, in a peak of about 100K, suggesting that two thirds of the total alpha-subunit in serum is present in the approximately 150K complex, and one third is uncomplexed. Development of this RIA for alpha-subunit will allow further study of regulation of the GH-dependent complex.

Long-term effects of insulin-like growth factor (IGF)-I on serum IGF-I, IGF-binding protein-3 and acid labile subunit in Laron syndrome patients with normal growth hormone binding protein

“…In normal individuals, ALS is present in excess, in molar terms, compared with IGFBP-3 (14). The ALS:IGFBP-3 molar ratio showed a marked decrease in the male siblings and an increase in the female, after 1 week of IGF-I treatment, becoming stable over the following weeks of treatment (Fig.…”

“…Normal values for IGFBP-3: 3-4 years -2:4 Ϯ 0:6 mg/l, range 1.2-3.5 mg/l; 10 years -3:6 Ϯ 0:7 mg/l, range 2.1-4.6 mg/l (13,17). Normal values for ALS: 3-4 years -14:2 Ϯ 6:0 mg/l, range 4-22 mg/l; 10 years -19:3 Ϯ 5:6 mg/l, range 9-28 mg/l (14). concentration was evident during long-term IGF-I treatment, with a twofold increase after 6 months of treatment ( Fig.…”

“…Sera were assayed for immunoreactive IGFBP-3 and ALS as described previously (13,14). The lower limit of detection of IGFBP-3 was 0.1 mg/l and that of ALS was 0.25 mg/l; the intra-and interassay coefficients of variation (CV) for IGFBP-3 were 6.2% and 11.9% (13) respectively, and those for ALS were 3.4% and 10.5% respectively (14).…”

“…The lower limit of detection of IGFBP-3 was 0.1 mg/l and that of ALS was 0.25 mg/l; the intra-and interassay coefficients of variation (CV) for IGFBP-3 were 6.2% and 11.9% (13) respectively, and those for ALS were 3.4% and 10.5% respectively (14). Serum IGF-I was measured by specific RIA as described previously (15).…”

Measurement of the acid-labile subunit of the insulin-like growth factor binding protein complex in human serum: a comparison of four immunoassays

“…Synthesis of the third member of the complex, ALS, appears to occur exclusively in the liver, and is similarly dependent on GH , with levels in the serum of hypophysectomized rats being less than 5% of those in normal controls (Fielder et al 1996). While serum ALS levels are also markedly GHdependent in humans (Baxter 1990), there has been limited detailed evaluation of the value of ALS as an index of GH secretory status or action, mainly because the assay has remained in very restricted use since its introduction in 1990 (Baxter 1997b). A variety of independent assay methods have recently become available, and this study was therefore designed to evaluate and compare their performance with serum samples from subjects in a variety of different physiological and pathological states.…”