Corticotropin in human plasma. General considerations.

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The demonstration of different corticotropin-related compounds occurring in the pituitary and additionally in other body tissues, of rapid metabolic degradation processes, of the dynamic feature of the ratio between immunoassayable and bioassayable corticotropin in human plasma, and of a distinct heterogeneity of ACTH-immunoreactive material in the circulation raises a number of questions with regard to the exact dimension of ACTH-related precursor and particularly metabolic products in blood, to the secretory sources and their regulation, and to their physiological meaning. At this point, there has only been a modest beginning in looking for answers to these questions. Nevertheless, it is justified to conclude that estimates of total ACTH immunoreactivity in human plasma do not necessarily reflect activity of pituitary ACTH secretion as generally assumed and that the dynamic dichotomy of immunoactive and bioactive ACTH in plasma reflects the presence of peptide molecules which are ACTH related but devoid of steroidogenic potency. It particularly remains to be elucidated whether all these degraded molecules are simply catabolic, biologically inactive products or whether they are partially biologically active with a potential spectrum of bioactivities different from that of the native molecule. We expect this to become a most interesting and rewarding area of research in the future.