Acid-Labile Subunit of Human Insulin-Like Growth Factor-Binding Protein Complex: Measurement, Molecular, and Clinical Evaluation

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Abstract
Although the acid-labile subunit (ALS) of the ;150-kDa insulin- like growth factor (IGF)-binding protein (IGFBP) complex was de- scribed over a decade ago, details of ALS physiology have remained largely uncertain. We evaluated antibodies to synthetic human ALS and constructed a noncompetitive ALS enzyme-linked immunosor- bent assay. Whereas uncomplexed ALS is directly measured, deter- mination of total levels required sample pretreatment with SDS, which was found to optimally dissociate complexed ALS and signif- icantly enhance ALS immunoreactivity. ALS in random adult sera was approximately 50% uncomplexed, and samples devoid of com- plexed ALS by immunoaffinity separation contained about 54% of the total levels. Serum ALS fractionated by gel filtration high perfor- mance liquid chromatography eluted in a single peak at approxi- mately 150 kDa with IGF-I and IGFBP-3, but appeared at about 400 -500 kDa after sample acidification and fractionation under acidic condition. The unexpected shift in ALS immunoreactivity re- mained unchanged when acid-neutralized or SDS-treated samples were fractionated under neutral pH and was reproducible when the 150-kDa complex was isolated, treated with acid or SDS, and rechro- matographed. ALS in adult sera more tightly correlated with IGFBP-3 than IGF-I or IGF-II. The total levels (mean 6 SD) were 16.7 6 3.7 mg/L in 22 normal subjects, 28.3 6 8.1 mg/L in 20 acro- megalic patients, and 9.5 6 3.8 in 32 GH-deficient adults. Little or no ALS was detectable in amniotic fluid, cerebrospinal fluid, seminal plasma, or milk, whereas high levels were present in synovial fluid. The development of ALS enzyme-linked immunosorbent assay should greatly facilitate further investigations of this unique glyco- protein. (J Clin Endocrinol Metab 82: 3944 -3951, 1997)

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