Modified forms of human growth hormone with increased biological activities.

Abstract

A proteolytically modified form of human growth hormone, isolated from a pituitary extract, had a growth promoting potency of 6.9 IU/mg in the tibial line assay. The prolactin activity of the material, measured by the crop sac assay, was 14.5 IU/mg. Peptide mapping indicated that residues 135–146 were missing from the large disulfide loop of the protein. Data are presented also for two other modified forms of the hormone. One lacked residues 135–140; the other was missing residues 135–145 together with a number of amino acids COOH-terminal to the cleavages. These latter two forms also showed a marked increase in prolactin activity and some potentiation of growth stimulating ability. All three forms were indistinguishable from intact growth hormone by radioimmunoassay and did not react with antiserum to human prolactin. These results indicate that the most active form of human growth hormone, as measured by the tibial line and crop sac assays, is not the intact hormone. (Endocrinology 94: 883, 1974)