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.

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.