ALS ELISA

Features

• RUO
• duration 3h
• 6 single standards: 0 – 200 ng/mL, native human ALS
• 2 control sera, freeze-dried
• Intra- / Interassay <10 %

Research topic

Growth hormone and factor-related products

Summary

The Insulin-like Growth Factors (IGF) – I and II are bound to specific binding proteins in circulation (IGFBP). Until today seven different proteins have been identified: IGFBP-1 to 7 [1, 2]. IGF bioavailability, transport and storage is regulated and facilitated by these binding proteins which are expressed differentially according physiological and developmental requirements. The most abundant IGFBP in circulation is IGFBP-3. Together with IGFBP-5 it is able to form the so called ternary complex with IGF and the acid-labile subunit (ALS) [3-5]. In the circulation nearly all IGF is bound in this ternary complex and thus not able to cross the endothelial barrier. Only very small amounts of IGF or IGFBP-3 exist outside this complex [6, 7]. The acid-labile subunit is an important part of the IGF-storage mechanism in circulation. In ALS deficiency or in ALS knock-out mice the concentrations of IGF and IGFBP-3 in the circulation are significantly decreased thus resulting in impaired growth [10]. The acid-labile subunit is synthesized as propeptide of 605 amino acids. The signal peptide, necessary for ALS secretion (AA 1-27) cleaved off enduring the transport process (Swiss- Prot P35858 Version 82). Thus the mature protein consists of 578 amino acids and contains about 20 leucin rich sequence repeats. Beside the leucin-rich repeats several potential Nlinked glycosylation sides are described. Miller BS et al. were able to demonstrate that incomplete glycolsylation of IGFs, ALS and IGFBP-3 results in a decreased serum concentration of these proteins. Oral mannose therapy resulted in a partial normalization of the glycosylation pattern and went along with improved growth [8]. Mutations in or the complete knock out of the ALS gene result in IGF / IGFBP-3 deficiency and therewith in disturbance of growth [9,10]. Beside growth also other endocrine axes may be involved. In primary ALS deficiency hyperinsulinemia could be observed [11, 12]. Further, the ALS-IGFIGFBP- system seems to be of relevance in coronary disease [13].

The results of this test system can be used as supplementary information in GH-diagnostics together with IGF-I and IGFBP-3 measurements. Thus, it is of use in evaluation of GHdeficiency and excess [14, 15] The first ALS immunoassay was described by Baxter RC in 1990 [6]. By this in-house radioimmunoassay it was shown that ALS is present in high concentrations in serum (50 μg/mL) of healthy humans. But not detectable in other body fluids like amniotic fluid, cerebrospinal fluid or seminal plasma – in spite of the fact that these body fluids contain high levels of IGFBP-3.