Previous work from this laboratory indicated significant elevations of cortisol after the administration of tryptophan. The current investigation was designed to confirm this observation and study the effect of this agent on ACTH. Cortisol rose 12.4 +/- 5.2 microgram/dl (mean +/- SD) in 10 of 12 tests (P less than 0.02). Responding patients had rises of ACTH averaging 101.8 +/- 45.8% (range, 40-159 pg/ml) above baseline. The time course of the ACTH change closely paralleled that of cortisol, and there were significant correlations between the rises of the two substances (r = 0.81; P less than 0.01). The current data strongly suggest that tryptophan administration stimulates ACTH release, possibly through activation of the central serotonergic nervous system. Review of the literature suggests the possibility that ACTH stimulation only occurs at high plasma tryptophan (and presumably brain serotonin) concentrations, with ACTH inhibition occuring at lower levels.

Tryptophan administration was used to evaluate the possibility that serotonergic neurons are involved in regulating the release of cortisol, renin, and aldosterone. Eleven studies were undertaken using 2 or 10 g tryptophan administered to fasting patients in continued supine posture. Aldosterone rose significantly to 208% (range, 128-329%) of baseline in all seven studies using 10 g and in one of the four studies using 2 g. Renin rose significantly to 189% (range, 116-340%) of baseline in four of the seven studies using 10 g and in two of the four studies using 2 g. Cortisol rose from 10.1 +/- 3.3 to 20.0 +/- 3.7 micrograms/100 ml (P less than 0.001 by t test) in six of the seven studies using 10 g and three of the four studies using 2 g. In eight studies, there was a significant rise of more than one substance after tryptophan administration. In six of these, peak values of the responding hormones occurred at the same time or within a single 30-min sampling interval despite the absence of a constant relationship between their rises. The results suggest participation of the central serotonergic nervous system in the control of renin and aldosterone in addition to its previously postulated role in cortisol release.