Failure of endogenous plasmin to convert human growth hormone to its "activated" isohormones

Human growth hormone B can be converted to its more acidic isohormones C, D, and E by limited enzymatic cleavage with purified plasmin in vitro. This process is accompanied by an increase of biological activity in the rat tibia line assay. A possible role of endogenous circulating plasmin in the in vivo formation of these isohormones was investigated. Human plasma, serum, glass-contact-activated serum, and serum extracts after the removal of protease inhibitors were incubated with ratioiodinated hGH-B and C for up to 24 h. Aliquots were analyzed at frequent intervals by polyacrylamide gel electrophoresis, followed by autoradiography and counting of radioactive bands. No evidence for interconversion or transformation to hGH-D and E was found. It is concluded that endogenous circulating plasmin does not play a major role in the conversion of hGH to its "activated" isohormones.