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A Specific Growth Hormone-Binding Protein in Human Plasma: Initial Characterization^*

GERHARD BAUMANN, MARK W. STOLAR, KLAUS AMBURN, CHARLES P. BARSANO and BRENT C. DEVRIES

Center for Endocrinology, Metabolism, and Nutrition, Department of Medicine, Northwestern University Medical School, and Veterans Administration Lakeside Medical Center Chicago, Illinois 60611

Address requests for reprints to: Dr. Gerhard Baumann, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611.

Human (h) GH in plasma exists as a series of size isomers, which are in partexplained by the presence of hGH oligomers. However, certain aspects of circulating largemol wt hGH, such as its high relative proportion compared to that in the pituitary, are poorly understood. To explore whether binding of hGH to plasma protein (s) could contribute to the phenomenon of large mol wt hGH, we incubated freshly prepared monomeric [¹²⁵I]hGH or biosynthesized ]³H]hGH with normal human plasma or serum atpH7.4 for various time periods at 22 and 37 C. Plasma radioactive hGH patterns were thenanalyzed simultaneously with unincubated tracer hGH by Sephadex G- 100 and G-200 chromatography. We found that part of the radioactivity was converted to a component with an apparent mol wt of 85,000, suggesting binding to a plasma protein(s). This phenomenon was inhibited in a dose-dependent fashion by unlabeled hGH. Saturation/Scatchard analysis indicatedan association constant (K_a) of 2–3 x 10⁸ M^–1 and amaximum binding capacity of 20 ng hGH/ml plasma. Binding was rapid, reversible, and specific. A number of polypeptide hormones, including human placental lactogen, hPRL and rat GH, did not inhibit hGH binding. However, the 20K variant of hGH interacted weakly with the plasma binding component (K_a, 1.2 x 10⁷ M^–1;maximum binding capacity, 450 ng/ml). The binding component was heat labile and could be partially purified by gel permeation chromatography and affinity chromatography on a hGH-Sepharosecolumn. Its estimated mol wt is 60,000–65,000, and it appears to bind one molecule of hGH to form a complex of 80,000–85,000 mol wt. The binding component is neither albumin rior animmunoglobulin. Under physiological conditions, a minimum of 15–18% of circulating hGH is presumably bound to this plasma component.

We conclude that a specific, high affinity, low capacity binding protein for hGH with mol wt of 60,000–65,000 exists in normal and hypopituitary human plasma. hGH complexed with this protein forms part of big-big hGH. The biological significance of this binding protein remains to be investigated.(J Clin Endocrinol Metab62: 134, 1986)

^* This work was reported in part in abstract form (Clin Res 33:567A,1985). This work was supported by NIH Grants AM-27047, AM-07169,AM-10699, RR-48, and RR-0537 and a grant from the V.A. Medical Research Service.

Recipient of a student award from the American Diabetes Association, Northern Illinois Affiliate.

Received June 11, 1985.

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