Stimulation of Aldosterone, Renin, and Cortisol by Tryptophan*

Abstract

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.

Central serotonergic stimulation of aldosterone secretion.

“…Unlike the stable PRA observed in the present study, Modlinger et al (4) found a rise in renin activity after oral tryptophan administration. Two studies in rats have also shown a stimulatory effect of serotonin and 5HTP on PRA (31, 32), and the stimulation appears to be peripherally mediated, as decarboxylase inhibition blocked the effect of 5HTP on PRA (32).…”

“…Our results are similar to those of Mantero et al (5), who reported no effect of intravenous serotonin administration on PRA. The discrepant PRA results between Modlinger's study (4) and our own may be explained by effects of other metabolites of tryptophan on renin secretion. Different levels of serotonin may also have been achieved in these studies, as postulated by Mantero (5).…”

“…Serotonin stimulates aldosterone secretion both in vitro and in vivo (1)(2)(3)(4)(5), and cyproheptadine, a serotonin antagonist, has been shown to decrease plasma aldosterone levels in patients with idiopathic aldosteronism (6). The mechanisms by which serotonin and cyproheptadine alter aldosterone secretion in vivo have not been established.…”

Urinary free cortisol secretion in habitually violent offenders

“…Also in man, 5-HTP increases plasma ACTH (3) and cortisol (3,4). Increased cortisol and ACTH after oral L-tryptophan have also been reported (5,6). The antiserotonin agents, metergoline and cyproheptadine, inhibit metyrapone-induced ACTH secretion (7, 8) and insulin hypoglycemia-stimulated cortisol secretion (9).…”

Paracrine control of steroidogenesis by serotonin in adrenocortical neoplasms

“…5-HT is also able to activate the renin angiotensin system which is a major regulator of aldosterone secretion. Clinical trials have shown an increase in plasma renin activity after administration of 5-HT precursors, 5-HT itself or 5-HT reuptake inhibitors to healthy volunteers and/or depressed patients (Ahmed et al, 2011;Mantero et al, 1982;Modlinger et al, 1979). The receptors that mediate the effect of 5-HT on renin production by the juxta-glomerular apparatus are not known in man.…”