THE BIOACTIVITY OF IMMUNOREACTIVE ADRENOCORTICOTROPHIN IN HUMAN BLOOD IS DEPENDENT ON THE SECRETORY STATE OF THE PITUITARY GLAND

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Abstract
SUMMARY: A highly sensitive bioassay, using preincubated purified isolated rat adrenal cells, has been developed for measuring plasma ACTH. This bioassay enables detection of ACTH in plasma of about 0.9 pmol/1. Bioactive ACTH (B‐ACTH) plasma levels were determined during insulin‐induced hypoglycaemia in 12 female subjects and the values were compared with immunoreactive ACTH (I‐ACTH) levels. The mean (|Mp SD) basal B‐ACTH level amounted to 1·7 ± 0·8 pmol/1, the mean I‐ACTH to 2·9 ± 1·4 pmol/1. The highest mean B‐ACTH plasma value was found 30 min after insulin injection: 14·7 ± 15·7 pmol/1 (I‐ACTH: 12·8 ± 9·9 pmol/1). By 90 min the B‐ACTH level had returned to baseline (1·6 ± 0·8 pmol/1), whereas the I‐ACTH level was still significantly higher (5·4 ± 2·7 pmol/1) than at time zero. Remarkably, the B‐ACTH to I‐ACTH ratio (B/I ratio) showed a biphasic profile during the insulin tolerance test, the ratio increasing from 0·60 ± 0·77 at time zero to 1·08 ± 0·35 at the ACTH peak, and decreasing after that to a lower value of 0·33 ± 0·11 at 90 min.From these results it is concluded: (1) in the morning hours a considerable amount of circulating I‐ACTH has no steroidogenic activity; (2) the B/I ratio temporarily increases immediately after insulin injection but gradually decreases afterwards to values half the baseline level at 90 min. Whereas this decrease at 90 min can be explained by differences in disappearance rates, the increase of B‐ACTH relative to I‐ACTH at 30 min indicates that estimations of immunoreactive ACTH reflect the biological activity of newly released ACTH with greater precision than at steady state level. Thus, the B/I‐ACTH ratio can be used as a tool for measuring the state of the pituitary releasing activity.