Stability of ACTH Preparations in Human Plasma Incubatedin Vitro

Abstract

The stability of the steroidogenic activity of ACTH was studied in human plasma incubated in vitro using a series of native and synthetic ACTH preparations. Native ACTH was stable over a period of 4 hr. when incubated in fresh human plasma, although it was significantly inactivated during the same period in plasma stored overnight in a freezer. Synthetic 39 amino acid ACTH ([alpha] p1-39-ACTH) was as stable as native ACTH in fresh plasma. However, synthetic preparations with 26, 19 and 18 amino acids ([alpha]b1-26-ACTH, [alpha]1-19-ACTH and [alpha]1-18-ACTH) were progressively less stable in that order, than was the whole molecule. Octadecapeptide amide (a1-18 NH2-ACTH) was significantly more stable than [alpha]1-18-ACTH. These results may explain at least partly the differences in steroidogenic potency of these ACTH preparations. It would appear, therefore, that the chain length of the C-terminal portion of the ACTH molecule is an important factor in protecting ACTH from inactivation. It suggests also that the presence of a carboxamide at the C-terminal may partially interfere with the enzymatic degradation of ACTH.