Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat

Henley, William N.; Chen, X.; Klettner, C.; Bellush, Linda L.; Notestine, Margaret A.

doi:10.1139/y91-030

Cited by 27 publications

(17 citation statements)

References 5 publications

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“…In this report, 5-HT and 5-HIAA were both increased in the majority of regions measured. Con sistent with this finding, we recently reported that surgical thyroidectomy in adult rats led to increased turnover of 5-HT(5-HIAA/5-HT) in the brain stem and spinal cord, which was normalized with T3 replacement [14].…”

mentioning

confidence: 69%

Streptozotocin-Induced Decreases in Serotonin Turnover Are Prevented by Thyroidectomy

Henley

Bellush²

1992

Neuroendocrinology

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Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/ 5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HTthrough the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with/7-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T₃, T₄ and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T₃ and T₄, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HTturnover.

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confidence: 69%

Streptozotocin-Induced Decreases in Serotonin Turnover Are Prevented by Thyroidectomy

Henley

Bellush²

1992

Neuroendocrinology

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“…53 observed an increase in the 5-HT precursor L-tryptophan (L-TP), and Heal and Smith 54 found an increase in both 5-HT and 5-HIAA in the midbrain after T 3 application in euthyroid animals. In contrast, Henley et al 42,45 examined animals after thyroidectomy, which resulted in an elevated serotonin turnover rate; in these animals, T 3 replacement resulted in a significant decrease in the 5-HIAA/5-HT ratio in the brainstem. In the two studies of thyroid replacement after thyroidectomy, T 3 replacement for longer than 3.5 days reduced the 5-HT turnover in caudal brainstem to completely normal values.…”

Section: Effects Of Thyroid Hormone Application On Brain Serotonin Symentioning

confidence: 99%

“…One early study measured brainstem 5-HT concentrations and did not find significant differences compared to euthyroid animals. 40 Later, using more sensitive assay techniques, five studies measured 5-HT and 5-HIAA concentration or the 5-HIAA/5-HT ratio as an indicator of the serotonin turnover and reported increased 5-HT metabolites in the brainstem [41][42][43][44][45] (notice: one study calculated the inverse ratio, 5-HT/5-HIAA 41 ). Reduced 5-HT concentrations in the cortex, 46,47 and reduced concentrations of the serotonin precursor 5-HTP were reported in the whole brain 48 of hypothyroid adult rats.…”

Section: Measurements Of 5-ht and Its Metabolites In Adult Hypothyroimentioning

confidence: 99%

Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain

2002

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The use of thyroid hormones as an effective adjunct treatment for affective disorders has been studied over the past three decades and has been confirmed repeatedly. Interaction of the thyroid and monoamine neurotransmitter systems has been suggested as a potential underlying mechanism of action. While catecholamine and thyroid interrelationships have been reviewed in detail, the serotonin system has been relatively neglected. Thus, the goal of this article is to review the literature on the relationships between thyroid hormones and the brain serotonin (5-HT) system, limited to studies in adult humans and adult animals. In humans, neuroendocrine challenge studies in hypothyroid patients have shown a reduced 5-HT responsiveness that is reversible with thyroid replacement therapy. In adult animals with experimentally-induced hypothyroid states, increased 5-HT turnover in the brainstem is consistently reported while decreased cortical 5-HT concentrations and 5-HT 2A receptor density are less frequently observed. In the majority of studies, the effects of thyroid hormone administration in animals with experimentally-induced hypothyroid states include an increase in cortical 5-HT concentrations and a desensitization of autoinhibitory 5-HT 1A receptors in the raphe area, resulting in disinhibition of cortical and hippocampal 5-HT release. Furthermore, there is some indication that thyroid hormones may increase cortical 5-HT 2 receptor sensitivity. In conclusion, there is robust evidence, particularly from animal studies, that the thyroid economy has a modulating impact on the brain serotonin system. Thus it is postulated that one mechanism, among others, through which exogenous thyroid hormones may exert their modulatory effects in affective illness is via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT 1A autoreceptors in the raphe area, and by increasing 5-HT 2 receptor sensitivity.

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“…Evidence for the interaction between serotonin (5-hydroxytryptamine, 5-HT) and thyroid hormones originates mostly from the experimentally induced hypothyroid state in animals [3]. Decreased 5-HT [7, 8] and increased 5-hydroxyinoleacetic acid [9] concentrations were observed in neonatal and adult hypothyroid rats, suggesting an increased 5-HT turnover [7, 10], while T 3 administration to hypothyroid animals normalized 5-HT turnover to normal values [10]. …”

Section: Introductionmentioning

confidence: 99%

Platelet Serotonin Concentration and Monoamine Oxidase Activity in Hypothyroid Patients

Stipčević

Kusačić-Kuna²,

Deželjin

et al. 2009

Horm Res Paediatr

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Background/Aim: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients. Methods: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T₄) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T₄ and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. Results: Hypothyroid patients had significantly higher TSH, significantly lower T₄ levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T₄ in control subjects. Conclusions: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure.

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Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat

Cited by 27 publications

References 5 publications

Streptozotocin-Induced Decreases in Serotonin Turnover Are Prevented by Thyroidectomy

Streptozotocin-Induced Decreases in Serotonin Turnover Are Prevented by Thyroidectomy

Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain

Platelet Serotonin Concentration and Monoamine Oxidase Activity in Hypothyroid Patients

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