Lack of in vivo transformation of human growth hormone to its "activated" isohormones in peripheral tissues of the rhesus monkey.

Human growth hormone (hGH) B can be transformed to its biologically more active isohormones C, D and E by limited proteolysis with plasmin in vitro, but the physiological significance of this observation is not known. The possible occurrence of such an "activation process" in peripheral tissues was investigated in the rhesus monkey. Radioiodinated hGH (B, C) or isolated hGH-B were injected intravenously into 4 rhesus monkeys and blood samples were drawn at frequent intervals. Analysis of circulating hGH was carried out by precipitation of hGH with trichloroacetic acid (TCA) and excess anti-hGH antibody, and by polyacrylamide gel electrophoresis followed by autoradiography. The metabolic clearance rate, based on TCA-precipitable radioactivity, was 2.36 +/- 1.17 ml/min/kg (mean +/- SD), similar to that reported for man. No evidence for the presence of circulating hGH-D or E was found, although progressive accumulation of smaller radioactive fragments and free iodide was observed. It is concluded that peripheral tissues or plasma enzymes probably do not convert significant amounts of hGH-B or C to their more active charge isomers, at least in the monkey. Therefore, if enzymatic activation of hGH does occur in vivo, the pituitary gland would seem the most likely site for such a process.