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The Effect of Circulating Growth Hormone-Binding Protein on Metabolic Clearance, Distribution, and Degradation of Human Growth Hormone^*

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

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

We recently described a specific binding protein for human GH (hGH) in human plasma, with which a substantial portion of circulating hGH is complexed. The biological function of the complexed fraction is unknown. To test the hypothesis that complexed hGH may have different in vivo kinetics than free hGH, we compared the MCRs, distribution volumes (V_d), and degradation rates of complexed and free [¹²⁵I] hGH in the rat. A partially purified GH-binding protein preparation, generated by affinity chromatography on a hGH column, was used for this purpose. A mixture of hGH with binding protein (equivalent to the amount contained in 0.9 mL human plasma) was injected iv as a single dose. Parallel experiments were conducted with hGH in the absence of binding protein. Disappearance of total, immunoprecipitable, and trichloroacetic acid-precipitable radioactivity from rat plasma was followed, and MCR, V_d, and degradation rates were derived by standard mathematical techniques. The MCR was 6-fold slower for com-plexed than for free hGH (2.3 vs. 14 mL/min·kg), V_d was 4-fold smaller for complexed hGH than for free hGH (71 vs. 256 mL/kg), and initial degradation rate was 4.5-fold lower for complexed than for free hGH (13.2% vs. 59.9%/15 min). The V_d of complexed hGH was close to the intravascular volume, while the Vd for free hGH corresponded to the extracellular volume. We conclude that one function of the hGH-binding protein is relative confinement of hGH to the vascular compartment, thereby protecting it from degradation and prolonging its biological half-life.

^* Presented at the 58th Annual Meeting of the Endocrine Society, Anaheim, CA, and reported in abstract form (Program of the 58th Meeting of The Endocrine Society, no. 11). This work was supported by NIH Grants RR-0537 and AM-10699 and a McGaw Medical Center Interinstitutional Research Grant.

Received August 7, 1986.

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