Substantial amounts of big IGF-II have also been found in cerebrospinal fluid, extracts of the brain and pituitary gland, and in the conditioned medium of several cell types (7).
Although the exact mechanism is still unknown, big IGF-II seems to possess properties that do not allow the proper formation of a 150-kDa complex with IGF-binding protein-3 (IGFBP-3) and the acid-labile subunit (14).
Initially, the detection of serum big IGF-II in the diagnosis of NICTH required size separation by, e.g., Bio-Gel P-60 acid gel filtration (13).
We report on the validation and application of this ELISA in the determination of big IGF-II in plasma samples of healthy individuals and patients with CRF and NICTH.
For the three NICTH patients investigated, most of the IGF-II IMR in plasma (65-78%) was associated with big IGF-II, whereas free E-domain fragments were hardly detectable.
This would explain, at least in part, the lack of increase in circulating total IGF-II [as determined by RIA with an antibody to IGF-II(1-67)] in NICTH patients, in spite of the high expression of the IGF-II gene and secretion of big IGF-II by these tumors.
For normal and NICTH plasma, as well as the sample of tumor cyst fluid, the major proportion of E(68-88) IMR eluted as big IGF-II because this peak also contained IGF-II(1-67) IMR.
Other than in NICTH, relatively little is known about the natural occurrence of big IGF-II in plasma and other biological fluids in health and disease.