Journal of Clinical Endocrinology & Metabolism, Vol 67, 265-272, Copyright © 1988 by Endocrine Society

ARTICLES

Characterization of the acid-labile subunit of the growth hormone- dependent insulin-like growth factor binding protein complex

RC Baxter
Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

The insulin-like growth factors (IGFs) circulate predominantly in a 150,000-dalton (150K) complex, the IGF-binding component of which appears to be an acid-stable 53K glycoprotein (BP-53). This study tested the hypothesis that an acid-labile subunit (ALS) reacts with the binding subunit to form the 150K complex. ALS activity was quantitated by the conversion of covalent BP-53-[125I]IGF-I tracer from about 60K to about 150K. DEAE-Sephadex chromatography of serum at pH 8.2 yielded separate peaks of 30-60K BP-53 immunoreactivity and 100-110K ALS which, when mixed, converted the BP-53 to 150K. Whole serum also contained 100- 110K ALS not complexed with BP-53. ALS was markedly acid labile, irreversibly losing activity below pH 4.5. In an assay involving competition between test substances and BP-53-IGF-I tracer in the reaction with partially purified ALS, serum samples, acidified to inactivate endogenous ALS, reacted with potencies proportional to their immunoreactive BP-53 content. Pure BP-53 alone was inactive, but after preincubation with IGF-I or IGF-II, competed with a potency identical to that of BP-53 in acidified serum. Amniotic fluid IGF-binding protein, with or without IGFs, had no activity. These results confirm that serum contains an acid-labile protein which interacts with the acid-stable IGF-binding protein BP-53, when it is occupied by IGFs, to convert it to the 150K form.

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