Complex Role of 5-HT in the Regulation of TSH Secretion in the Male Rat

Abstract

The role of 5-hydroxytryptamine (5-HT) in the regulation of TSH secretion was studied in male rats using both peripheral and central administration of the drugs. Basal TSH levels were not modified by moderate doses of 5-HT (subcutaneously) or its precursors or antagonists (intraperitoneally) given 1 h before decapitation. The cold-stimulated TSH secretion was decreased by L-tryptophan (L-TRP, 400 mg/kg i.p.), quipazine (10 mg/kg i.p.) and 5-HT (1 or 5 mg/kg s.c. or i.v.) as well as by p-chlorophenylalanine (pCPA, 20 or more mg/kg i.p.) when the drugs were given 1 h before sampling. pCPA (100–400 mg/kg i.p.) was active 24-48 h after the injection but repetitive administration did not affect TSH levels. 5-HT (5 mg/kg s.c.) was effective also in pinealectomized animals. L-TRP and 5-hydroxytryptophan potentiated the TRH-stimulated TSH secretion when given 1 h before killing. 5-HT (10 µg/rat) infused into the third ventricle enhanced the cold-stimulated TSH secretion when given 30-45 min before sampling. When injected into the medial basal hypothalamus, 5-HT (1-10 µg/rat) had no effect on basal or stimulated TSH levels. The results suggest: (1) 5-HT does not play any role in the regulation of basal TSH secretion; (2) in the cold-stimulated TSH secretion 5-HT has a stimulatory action evidently inside the blood-brain barrier and also an inhibitory effect obviously outside this barrier.

Neurotransmitter Control of Thyrotropin Secretion

“…In contrast, tryptophan, another precursor of 5HT, was reported to have inhibitory influence on TSH secretion by several authors [71,83,86]. Results obtained with the blocker of serotonin synthesis, />-chlorophenylalanine are also difficult to fit into any con sistent pattern.…”

“…Jordan et al [48] and Fukuda et al [36] claim that de pletion of brain serotonin eliminates the daily peak of TSH occurring around noon but has no effect on TSH levels at other times of the day. The complexity of the serotonergic regulation of TSH secretion is well documented by a recent paper by Maltila and Mannisto [71] as well as by Morlev et al [84]. * There are only a handful of clinical studies of serotonin in relation to TSH secretion.…”

Central Serotoninergic Stimulation by Fenfluramine Challenge Does Not Affect Plasma Thyrotropin-Stimulating Hormone Levels in Man

“…Data from animal studies support both stimulatory and inhibitory roles for this neurotransmitter. Stimulation of TSH release by 5-HT has been suggested in studies em ploying intraventricular injection of 5-HT [17,18,39] and intraventricular and parenteral administration of the 5-HT precursor 5-hydroxytryptophan (5-HTP) [5,32] and the 5-HT synthesis inhibiting p-chlorophenylalanine [5,33], Con versely, inhibition of TSH release by 5-HT has been sugges ted in studies employing inirahypothalamic implants or in traventricular injection of 5-HT [15,23] and intraventricular or parenteral administration of the 5-HT agonist quipazine [19], the 5-HT-releasing ¿/-fenfluramine [8,9], the 5-HT pre cursor tryptophan [22,24,25], and p-chlorophenylalanine [31]. Further, studies employing 5-HTP suggest that 5-HT inhibits cold-induced activation of TSH [27,37].…”

Site-Dependent Action of Intracerebroventricular 5-Hydroxytryptamine on the Cold-Stimulated Thyrotropin Secretion in Male Rats

“…Our laboratory has previously reported both inhibitory, al though not significant [26], and stimulatory [22,25] effects of 5-HT on TSH levels in separate sets of experiments using the same coordinates for stereotaxic infusions into the third ventri cle. These coordinates are approximately 2.5 mm caudal and I. I mm rostral to the ones applied for the anterior and poste rior third ventricle in the present study, respectively.…”

“…However, in some reports, even eleva tions of basal [13. 14] and cold-stimulated [22] TSH levels have been reported after intracerebroventricular (i.c.v.) injections of 5-HT.…”