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

Abstract

The role of serotonin (5-HT) in the hypothalamic regulation of human growth hormone (GH) was reassessed through the use of fenfluramine, which selectively releases 5-l·lT from presynaptic terminals. Oral administration of L-dopa plus propranolol induced a potent and sustained GH release in the subjects tested (26 ± 6 ng/ml). The administration of fenfluramine (20 mg i.v. as bolus plus 20 mg/30 min i.v.) completely suppressed the L-dopa-induced GH secretion (2 ± 0.5 ng/ml). On the other hand, when arginine (30 g/30 min i.v.) was used as a GH stimulant of medium intensity (12.7 ± 2.8 ng/ml), fenfluramine at the same dose was not able to alter the pattern of pituitary secretion (11.5 ± 4.2 ng/ml). Fenfluramine alone induced a slight nonsignificant decrease in GH values with a parallel and significant increase in prolactin (PRL) secretion in accordance with the proposed serotoninergic activity of the drug. Rat PRLsecretion by pituitaries incubated in vitro was inhibited by dopamine. Fenfluramine added to the system did not counteract the dopaminergic reduction of PRL release, making unlikely the possibility of an antagonism at the dopaminergic receptor as mechanism of action of fenfluramine on PRL secretion. In conclusion, depending on the stimulus under study, serotoninergic activation by fenfluramine either inhibits or does not alter GH secretion in man. No proof of a serotoninergic stimulatory component on GH regulation has been detected in this study. Fenfluramine is a valuable tool in neuroendocrinological studies, dealing with serotoninergic mechanisms.

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

“…Alternatively, MCP might also activate serotoninergic pathways [18], but this seems to be devoid of signifi cant effects on GH release in man [19], As in our previous data [12], when GHRH was given after placebo, GHRH-elicited GH peaks were closely related to the functional status of the somatotrophs at the time of this challenge. Nevertheless, this was not observed in the ex periments in which MCP was given prior to or together with the GHRH bolus.…”

Influence of Different Serotonin Receptor Subtypes On Growth Hormone Secretion

“…However, a stimulatory role of 5-HT on cGH release has also been suggested, based on the finding that activation of 5-HT neurotransmission with 5-hydroxytryptophan (5-HTP) increases plasma GH levels [31]. Finally, as happened with dogs, based on data obtained in humans, stimulatory, inhibitory or no influence of serotoninergic pathways have been claimed [3, 4, 5, 7, 9, 10, 11]. However, in light of the poor specificity of most of the drugs used in these studies, it was concluded by most authors that no firm conclusions could be reached [1, 2].…”

“…Although in the last two decades considerable insight has been gained with regard to the role played by different neurotransmitter pathways, the mechanisms underlying the serotoninergic control of GH secretion are not yet clear, with stimulatory, inhibitory or no effect having been reported [3, 4, 5, 6, 7, 8, 9, 10, 11, 12]. This limitation has mainly been due to the existence of many different receptors that mediate the serotonin (5-HT) actions, and the lack of suitable specific agonist and antagonist drugs.…”

Effects of Clonidine on Blood Pressure, Noradrenaline, Cortisol, Growth Hormone, and Prolactin Plasma Levels in High and Low Intestinal Tone Depressed Patients

“…In this respect, the fact that both CRT and PRL mean plasma levels were greater in high-IT depressed patients than in low-IT depressed patients, during pre-clonidine pe riods, suggests the stimulating role that the serotonergic system might play in releasing these hypothalamic factors in the former group. In effect, it is a well-known fact that the central serotonergic system is involved in the releasing of corticotrophin-releasing hormone and triggers PRLreleasing mechanisms [3,9,20,22,24,25,31]. Furthermore, the proven fact that fenfluramine (a serotonin depletor agent) [10] is able to induce a quick improvement of high-IT depressed patients [18] provides additional reinforcement to this presumption.…”