Evidence that the Effects of 5-Hydroxytryptophan on the Secretion of ACTH and Growth Hormone in Dogs are not Mediated by Central Release of Serotonin

Abstract

5-Hydroxytryptophan (5-HTP) was found to lower plasma 11-oxycorticoids and increase plasma growth hormone in anesthetized dogs. To determine whether these effects were mediated by release of serotonin, 5-HTP and L-tryptophan were injected intravenously alone and after treatment with various drugs. The decrease in corticoids produced by 5-HTP was unaffected by intravenous carbidopa and metergoline, but was abolished by intravenous benserazide in a dose that inhibits central 5-HTP and dopa decarboxylase, and by a small dose of phenoxybenzamine in the third ventricle. Adrenal sensitivity to ACTH was unaffected by 5-HTP. L-Tryptophan did not decrease plasma corticoids; instead it produced a small increase. The increase in plasma growth hormone produced by 5-HTP was potentiated by carbidopa and abolished by benserazide. L-Tryptophan did not increase plasma growth hormone; instead it produced no change or in some instances a decrease. Plasma growth hormone declined after administration of phenoxybenzamine in the third ventricle, and the decline continued after administration of 5-HTP. The data indicate that the effects of 5-HTP on ACTH and growth hormone secretion are not due to central release of serotonin and suggest that they are due instead to serotonin-induced release of catecholamines from catecholamine-secreting neurons.

Depending on the Stimulus, Central Serotoninergic Activation by Fenfluramine Blocks or Does not Alter Growth Hormone Secretion in Man

“…29]. Recently, results have been reported in dogs that are consistent with the hypothesis that the GH stim ulating activity of 5-HT is due to central release of catecholam ines from the catechol amine-secreting neurones rather than serotonin from the serotoninergic ones [48]. A similar lack o f GH-releasing action has been reported in man using quipazine, a direct 5-HT receptor stim ulant [36].…”

Aromatic <i>L</i>-Amino Acid Decarboxylase Activity in the Rat Median Eminence, Neurointermediate Lobe and Anterior Lobe of the Pituitary

“…and DA content. Furthermore, the results implicate a central source(s) in supplying a large portion of the 5-HIAA found in the animal's own AP, and suggest that although the contribution of centrally synthesized 5-HT to basal AP 5-HT concentra tions may not be a major one, under circumstances where central L-AAD-containing areas are greatly stimulated, the newly synthesized 5-HT can affect 5-HT concentrations in the AP.L-5-hydroxytryptophan (5-HTP), the immediate amino acid precursor of the neurotransmitter, 5-hydroxytrypt amine (5-HT), has been employed in several experimental paradigms in an attempt to ascertain the role of 5-HT neu ronal systems in various neural and neuroendocrine func tions [13,22,25]. Recent evidence indicating that 5-HT can enhance basal and arginine vasopressin-stimulated adreno corticotropic hormone release directly from dispersed ante rior pituitary (AP) cells [18] emphasizes the importance of identifying possible sources which could supply 5-HT to the AP.…”