Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

Authors: Y Shenker, M D Gross, R J Grekin
Keywords: aldosterone production, serotonin antagonism
DOI Number: 10.1172/JCI112128      Publication Year: 1985

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