Sleep deprivation alters thyroid hormone economy in rats.

NEW FINDINGS: What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all sleep-deprived and sleep-restricted rats; rebound restored this parameter in only the PSD24R group. The serum TSH and T4 concentrations decreased, whereas T3 increased in both the PSD24 and PSD96 groups compared with control animals (P < 0.05). Only PSD24R and PSD96R normalized T4 and thyroid-stimulating hormone concentrations, respectively, independently of the higher circulating T3 concentrations (∼20-30%) noted in all groups compared with control animals (P < 0.05). Brown adipose tissue D2 activity increased in the PSD 24 and 96 h groups (∼10 times), and PSD24R was more effective than PSD96R at restoring basal brown adipose tissue D2 activity. Our data suggest that thyroid hormone metabolism adapts to sleep deprivation-induced hypothalamic-pituitary-thyroid alterations and increases T4 to T3 activation peripherally, thereby increasing circulating T3 in rats.

Sexual dimorphism in autonomic changes and in the renin-angiotensin system in the hearts of mice subjected to thyroid hormone-induced cardiac hypertrophy.

Based on the relevance of the renin-angiotensin system and the ongoing controversy regarding the role of the sympathetic nervous system in thyroid hormone-induced cardiac hypertrophy, the aim of the present study was to establish whether the putative difference in the degree of cardiac hypertrophy exhibited by males and females might be related to differences in the sympathetic-vagal balance and/or in the cardiac renin-angiotensin system in mice of different genders. Male and female mice (n = 117) were given 0.1 mg kg(-1) of triiodothyronine or normal saline each day for 10 days consecutively. At the end of that period, study of the heart rate variability, spectral analysis and histopathological examination were performed to assess the sympathetic-vagal balance and the diameter of cardiomyocytes. The cardiac levels of angiotensin I and II were also measured. Treatment with triiodothyronine induced a greater degree of cardiac hypertrophy in male (~73%) than in female mice (~42%). This difference was attributed to greater modulation of the sympathetic nervous system and higher levels of angiotensin I and II in male than in female mice. Our data indicate that thyroid hormone-induced cardiac hypertrophy was more intense in male mice due to the synergic effect of the sympathetic nervous system and the cardiac renin-angiotensin system.

Retinoic acid modulation of thyroid dual oxidase activity in rats and its impact on thyroid iodine organification.

The sodium-iodide symporter (NIS) mediates iodide uptake into the thyrocytes, which is important for the diagnosis and therapy of thyroid disorders. Decreased ability to uptake iodide in thyroid carcinomas reduces the efficacy of radioiodine therapy, and retinoic acid (RA) treatment reinduces iodide uptake. The effectiveness of treatment depends not only on iodide uptake but also on the ability of thyrocytes to organify iodine, which is catalyzed by thyroperoxidase (TPO) in the presence of H(2)O(2). Our goal was to determine the influence of RA on thyroid iodide uptake, iodine organification, and TPO and dual oxidase (DuOx) activities. Normal rats were treated with all-trans-RA or 13-cis-RA (100 or 1500 microg/100 g body weight (b.w.), s.c.) for 14 and 28 days. The 2 h thyroid radioiodine content significantly decreased in rats treated with all-trans-RA (100 microg/100 g b.w.) for 14 days. In this group, NIS function and TPO activity were unchanged, whereas DuOx activity was significantly decreased, which might have contributed to the decrease in iodine organification. Both doses of 13-cis-RA for 28 days increased the 15 min thyroid radioiodine uptake, while the 2 h radioiodide uptake increased only in rats treated with the highest dose of 13-cis-RA. While TPO activity did not change, H(2)O(2) generation was increased in this group, and serum thyroxine levels were normal. Since radioiodine half-life in the thyroid gland is important for treatment efficacy, our results highlight the importance of correctly choosing the RA isomer, the time and the dose of treatment, in order to improve the efficacy of radioiodine therapy.

Retinoic acid effects on thyroid function of female rats.

AIMS: Retinoic acid is widely used in dermatological treatment and thyroid cancer management; however its possible side-effects on normal thyroid function remains unknown. We aimed to determine the effects of retinoic acid on thyroid function of adult female rats. MAIN METHODS: Female Wistar rats were treated with all-trans-retinoic acid and 13-cis retinoic acid for 14 and 28 days. Then, rats were killed and thyroid function was evaluated. KEY FINDINGS: Serum T4 and thyrotropin levels remained unchanged, while serum T3 increased in animals treated with all-trans-retinoic acid for 14 days. No changes were observed in hepatic or renal type 1 iodothyronine deiodinase (D1) activities, while thyroid D1 was higher in animals treated for 14 days with all-trans-retinoic acid, which could be related to the increased serum T3 levels. 13-cis retinoic acid increased thyroid iodide uptake after 28 days. These results show effects of retinoic acid treatment on these thyroid proteins: sodium/iodide symporter and deiodinase. SIGNIFICANCE: Retinoic acid is able to interfere with normal thyroid function, increasing thyroid type 1 deiodinase activity, serum T3 levels and sodium/iodide symporter function. However, the effects are time- and retinoic acid isomer-dependent. Since serum thyrotropin levels did not change in any group, the effects observed are probably mediated by a direct retinoic acid effect on the normal thyroid.

The effect of acute exercise session on thyroid hormone economy in rats.

The hypothalamic-pituitary-thyroid axis is affected by acute exercise, but the mechanisms underlying thyroid function changes after exercise remain to be defined. The aim of this study was to elucidate the effects of a session of acute exercise on the treadmill at 75% of maximum oxygen consumption on thyroid function of rats. Male Wistar rats were divided into five groups: control (without exercise), and killed immediately after (0 min) or 30, 60, and 120 min after the end of the exercise session. A significant increase in serum tri-iodothyronine (T(3)) occurred immediately after the exercise, with a gradual decrease thereafter, so that 120 min after the end of the exercise, serum T(3) was significantly lower than that in controls. Total thyroxine (T(4)) increased progressively reaching values significantly higher than that in the control group at 120 min. T(3)/T(4) ratio was significantly decreased 60 and 120 min after the exercise, indicating impaired T(4)-to-T(3) conversion. Liver type 1 deiodinase activity (D1) significantly decreased at 60 and 120 min, while pituitary D1 increased progressively from 30 to 120 min after the exercise, and thyroid D1 was increased only immediately after the end of the exercise. Brown adipose tissue (BAT) type 2 deiodinase activity (D2) was significantly lower at 30 min, but pituitary D2 remained unchanged. No change in serum thyrotropin was detected, while serum corticosterone was significantly higher 30 min after the exercise. Our results demonstrate that decreased liver D1 and BAT D2 might be involved in the decreased T(4)-to-T(3) conversion detected after an exercise session on the treadmill.

Low replacement doses of thyroxine during food restriction restores type 1 deiodinase activity in rats and promotes body protein loss.

During food restriction, decreased basal metabolic rate secondary to reduced serum thyroid hormones levels contributes to weight loss resistance. Thyroxine (T(4)) and 3,3',5-tri-iodothyronine (T(3)) administration during caloric restriction produce deleterious side effects; however, the administration of physiological doses of T(4) during food restriction has never been evaluated. The aim of this study was to analyze the effects of low replacement doses of T(4) in Wistar rats subjected to 40% food restriction. Food restriction for 30 days led to significantly reduced liver type 1 deiodinase activity, serum TSH, leptin, T(4), T(3), metabolic rate, and body mass. The significant reduction in hepatic deiodinase activity found during food restriction was normalized in a dose-dependent manner by T(4) replacement, showing that decreased type 1 deiodinase (D1) activity is secondary to decreased serum thyroid hormone levels during caloric restriction. The lowest replacement dose of T(4) did not normalize resting metabolic rate, but was able to potentiate the effects of food restriction on carcass fat loss and did not spare body protein. The highest dose of T(4) produced a normalization of daily oxygen consumption and determined a significant reduction in both carcass fat and protein content. Our results show that serum T(4) normalization during food restriction restores serum T(3) and liver D1 activity, while body protein is not spared. Thus, decreased serum T(4) during caloric restriction corresponds to a protective mechanism to avoid body protein loss, highlighting the importance of other strategies to reduce body mass without lean mass loss.