Slow Metabolic Clearance Rate of the 20,000-Dalton Variant of Human Growth Hormone: Implications for Biological Activity*

The 20,000-dalton variant of human GH (hGH) (20 K) exhibits full growth-promoting bioactivity in the rat despite its poor interaction with GH receptors, as compared to the principal 22,000-dalton form of hGH (22 K). To test the possibility that prolonged survival time of 20 K in vivo may contribute to this apparent discrepancy, we compared the MCRs of 22 K and 20 K in the rat by the single injection technique. Both radiolabeled and native 22 K and 20 K were examined in this regard. The MCR of 20 K was 2- to 3-fold lower than that of 22 K, a statistically significant difference (P less than 0.05). The distribution volumes were similar for the two hGH forms and corresponded approximately to the extracellular fluid space. We conclude that the prolonged persistence of 20 K in the circulation may contribute to its higher than expected bioactivity in vivo in the rat.