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Characterization of the Acid-Labile Subunit of the Growth Hormone-Dependent Insulin-Like Growth Factor Binding Protein Complex^*

ROBERT C. BAXTER

Department of Endocrinology, Royal Prince Alfred Hospital Camperdown, New South Wales 2050, Australia

The insulin-like growth factors (IGFs) circulate predominantly in a 150,000-dalton (150K) complex, the IGFbinding 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 acidlabile 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,

^* This work was supported by the National Health and Medical Research Council of Australia.

To whom requests for reprints should be addressed.

Received December 28, 1987.

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