Functions and regulation of the acid-labile subunit of the 150 K complex.
In normal subjects, the major form of circulating IGF is the GH-dependent 150 K complex. As demonstrated by gel-permeation chromatography, the acid-labile subunit (ALS) purified from human serum, incubated for 2 h at 20 degrees C with [125I]IGF-I and rIGFBP-3, is able to increase not only the molecular weight (mol. wt.) of the IGF-IGFBP-3 complex, but also the amount of IGF-I bound. In both charcoal and polyethylene glycol ligand binding assays, competitive binding curves for the displacement of [125I]IGF-I from rIGFBP-3 by increasing concentrations of unlabeled IGF-I showed an increased binding activity of rIGFBP-3 in the presence of ALS. The effect of ALS on rIGFBP-3 binding activity was dose dependent. In addition, ligand and immunoblot revealed that ALS and rIGFBP-3 are able to form a high mol. wt. complex in the absence of IGF peptide. On the basis of these data, ALS seems to have a more complex function than that of simply increasing the mol. wt of the IGF-IGFBP-3 complex. The regulation of ALS synthesis by rat hepatocytes in primary culture has also been evaluated by immunoblot. In agreement with the in vivo finding of an inhibitory effect of octreotide (a somatostatin analog) on the formation of the 150 K complex in acromegalic subjects, we could observe in vitro that octreotide produces a dose-dependent inhibition of ALS secretion into the hepatocyte conditioned medium. TGF-beta 1 was also inhibitory at high doses. On the contrary, we could not evidence any effect of IGF-I or IGF-II, while a small increase has been noted after incubation with T3.
Barreca
A
A
Department of Endocrinology and Metabolism, Institute of General Physiology, University of Genova, Italy.
Ponzani
P
P
Arvigo
A
A
Voci
A
A
Giordano
G
G
Minuto
F
F
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D015282:Octreotide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013002:Somatomedins / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D013002:Somatomedins; D016212:Transforming Growth Factor beta; C075944:insulin-like growth factor binding protein, acid labile subunit; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D015282:Octreotide