The role of thyroid hormone in sleep deprivation

Sleep deprivation is a stressful condition, as the subject experiences feelings of inadequate well-being and exhibits impairments in his/her functioning. However, in some circumstances sleep deprivation may be crucial for survival of the individual. Most likely, complex neural circuits and hormones play a role in allowing sleep deprivation to occur. For instance, thyroid hormone activity sharply increases when an individual is in a state of sleep deprivation. We believe that this increase is central to sleep deprivation physiology. During sleep deprivation, the hypothalamic–pituitary–thyroid axis initially increases as a consequence of increased release of thyroid stimulating hormone from the pituitary. Subsequently, as sleep deprivation continues, the sympathetic nervous system is recruited through its anatomical connection with the thyroid gland. While thyroid stimulating hormone levels markedly increase during sleep deprivation, it has been suggested that these increases are secondary to sleep deprivation. However, there is little evidence to support this assumption. We believe that the physiology of the thyroid axis during sleep deprivation and the actions of the effector hormone thyroid hormone suggest that thyroid hormone inhibits sleep and not the contrary. To our knowledge, few studies have addressed the possible neural functions that enable sleep deprivation. In this article, we discuss the hypothesis that an augmentation in the thyroid hormone axis is central to a subject’s ability to curtail sleep.     

Altered polyvinylpyrrolidone clearance and immune responsiveness caused by small dietary changes.

The introduction of 25 mg of a new protein antigen into the diets of mice produced transient increases in PVP clearance which reached a maximum 60 hr after the change of diet and had disappeared by 4 days. At the same time the immune responsiveness to unrelated antigens given parenterally was also raised transiently, reaching a peak 5 days following the change and disappearing by 7 days. In contrast the responsiveness to the fed antigen was diminished.     

Sexually dimorphic age-related changes in the distribution of immunoreactive luteinizing hormone releasing hormone in the platyfish

In this study on platyfish we demonstrate that the distribution and intensity of immunoreactive luteinizing hormone releasing hormone (ir-LHRH) in the brain and pituitary gland fluctuate at specific ages between 8 and 30 months. These changes are not the same in males and females, and they vary for each LHRH-containing region in the brain. In males, ir-LHRH intensity is greatest in the nucleus olfactoretinalis (NOR), nucleus preopticus periventricularis (NPP) and nucleus lateralis tuberis (NLT) at 18 months of age. In females, by comparison, the NOR displays the same degree of immunoreactivity at all ages examined, as does the NLT, where ir-LHRH perikarya are absent at all ages and immunoreactivity is restricted to a few fibers. In the NPP, females show fluctuations similar to those seen in males, however, the intensity of ir-LHRH is always less, and the number of ir-LHRH perikarya appear to be fewer, than in males. Thus, the age-related changes in LHRH systems in platyfish follow different patterns in males and females. Our study clearly indicates that immunocytochemical data must be evaluated with caution and that only after the age and sex of the animal and the maturational state of the gonads have been carefully scrutinized, can meaningful interpretations be made.     

Failure of dietary restriction to retard age-related neurochemical changes in mice

Age-sensitive neurochemical measures and estrous cyclicity were studied in female mice from the long-lived C3B10F₁ strain fed either a control diet or subjected to dietary restriction (DR) from 3 weeks of age. Striatal dopaminergic D2 receptor density decreased by 25% from 9–10 months to 28–30 months of age in the the control group. This decline was uninfluenced by DR. Anterior pituitary dopamine + dihydroxyphenylacetic acid content increased by 2.5 fold with age in the control group but DR failed to oppose this age-related change. In contrast to DR's lack of influence on these two neurochemical measures were findings on estrous cyclicity. Although mice on DR did not display estrous cycles, cyclicity was rapidly initiated when these mice were switched to the control diet at 12 and even at 22 months of age. Thus, limited aspects of neuroendocrine aging were retarded by DR in this long-lived mouse model.     

The role of stimulus type in age-related changes of visual working memory

Aging is accompanied by increasing difficulty in working memory associated with the temporary storage and processing of goal-relevant information. Face recognition plays a preponderant role in human behavior, and one might therefore suggest that working memory for faces is spared from age-related decline compared to socially less important visual stimulus material. To test this hypothesis, we performed working memory (n-back) tasks with two different visual stimulus types, namely faces and doors, and compared them to tasks with primarily verbal material, namely letters. Age-related reaction time slowing was comparable for all three stimulus types, supporting hypotheses on general cognitive and motor slowing. In contrast, performance substantially declined with age for faces and doors, but little for letters. Working memory for faces resulted in significantly better performance than that for doors and was more sensitive to on-line manipulation errors such as the temporal order. All together, our results show that even though face perception might play a specific role in visual processing, visual working memory for faces undergoes the same age-related decline as it does for socially less relevant visual material. Moreover, these results suggest that working memory decline cannot be solely explained by increasing vulnerability in prefrontal cortex related to executive functioning, but indicate an age-related decrease in a visual short-term buffer, possibly located in the temporal cortex.     

Neurosecretion in the hypothalamic nuclei and the changes in the concentration of thyroid hormone

Summary A study was made of changes in the rate of secretion in the supra-optic and paraventricular nuclei of rabbits in relation to thyroid concentration in the body. Changes in the hormonal balance were induced by thyroidectomy and by the administration of thyroidine or of 6-methylthiouracil.Hypothalamic secretion in the control animals was fluctuating, i.e., a phase of secretion was followed by one of evacuation and a shift of the secretory granules into the neurohypophysis. Accordingly the main mass of neurosecretion was present either in the cells of the paraventricular and supra-optic nuclei and in the median eminence, or in the posterior hypophyseal lobe.Treatment with thyroxin for 10 days led to an intensified production of the secretion in the hypothalamic nuclei, and to its accumulation in the neurohypophysis. Thyroidectomy or administration of 6-methylthiouracil decreased secretory activity by the cells, and caused a reduction in the store of neurosecretion in the posterior hypophyseal lobe.(Presented by Active Member AMN SSSR A. V. Lebedinskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 58, No. 7, pp. 102–106, July, 1964     

The effects of dietary vitamin E and selenium deficiencies on plasma thyroid and thymic hormone concentrations in the chicken

Beginning at hatching, male Cornell K strain single comb white leghorn chickens were fed a basal diet, with or without vitamin E (100 IU/kg) and/or selenium (Se, 0.2 ppm). After 3 weeks of treatment, animals fed either the Se-deficient or basal diet had significantly reduced plasma Se-dependent glutathione peroxidase activities when compared to those fed a vitamin E and Se-supplemented diet. Similarly, animals fed the vitamin E-deficient or basal diet had significantly reduced plasma alpha-tocopherol levels. The effect of these treatments on plasma concentrations of thyroid hormones (T(3)/T(4)), growth hormone (GH), and thymic hormone (thymulin) was determined using radioimmunoassay and ELISA. A deficiency in Se, but not in vitamin E, resulted in an increase in plasma T(4) concentrations while plasma T(3) concentrations were decreased. Plasma GH levels showed some fluctuation as a result of the dietary treatments but there was no significant correlation between plasma GH levels and any of the other variables. A significant decrease in plasma thymulin levels was observed in Se-deficient birds compared to those receiving adequate Se in the diet. A vitamin E deficiency had no measurable effect on plasma thymulin levels. From these studies, we conclude that plasma thymulin concentrations directly correlate with plasma T(3) concentrations which are negatively affected by a Se deficiency.     

The role of age-related factors in the effect of long-term perfusion on the contractility of isolated heart

Experiments on isolated hearts of mature and senescent rats showed that in mature rats the heart contractility decreased to a greater extent during the initial hours of a long-term perfusion, but in mature heart tolerance to perfusion was higher. Creatine phosphokinase activity drastically increased in the perfusate of senescent hearts and changed insignificantly in the perfusate of mature hearts. In mature rats a long-term perfusion was accompanied by activation of Na,K-ATPase, which was prevented by actinomycin D. Transfer of perfusate in the donor-recipient double-heart experiments with prior administration of actinomycin D showed that long-term perfusion induces the synthesis of a regulator factor (inverter) in the heart of mature rats which modulates myocardial contractility. This regulator peptide contributes to adaptive potency of the heart in mature animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 7, pp. 505–509, November, 1998     

The role of brain thyroid hormones in the mechanisms of seasonal changes in mood and behavior

Many individuals experience seasonal changes in mood and behavior. Various theories have been suggested to explain the mechanisms of these changes. However, the mechanisms of seasonal mood and behavioral changes remain unclear. The author suggests that brain thyroid hormones may play an important role in seasonal changes in mood and behavior. This suggestion is based on the facts that seasonal changes in light and temperature may affect the metabolism of brain thyroid hormones and that small alterations of the brain thyroid economy, independent of peripheral changes in thyroid status, may produce significant behavioral effects. The author further suggests that there may be a fault in the thyroid metabolism in the brain in seasonal affective disorder patients, and that fault cannot be identified by studying the peripheral thyroid hormone metabolism. Seasonal mood and behavioral changes may also be related to the interaction between thyroid hormones and different neurotransmitter systems in the brain.     

The role of triiodothyronine-induced substrate cycles in the hepatic response to overnutrition: thyroid hormone as an antioxidant

Overnutrition, by generating reactive oxygen species (ROS), produces oxidative stress - an important cause of cellular injury. In the liver, overnutrition begins in the perivenous hepatocytes. To prevent injury, cells must protect themselves against ROS accumulation. Overnutrition also activates the enzyme deiodinase-1 (D1), which catalyzes the conversion of T4 to T3. D1 is primarily located in the PV region of the liver. Thyroid hormone is known to generate substrate cycling. The hypothesis of this paper is that a nutrient-induced increase in intracellular T3 acts as an antioxidant by inducing substrate cycles that reduce ROS accumulation. These cycles do this by: (i) reducing ROS formation by hydrolyzing excess ATP, thus enhancing oxidative phosphorylation and reducing the proton motive force on the electron transport chain (ETC), and; (ii) enhancing the removal (reduction) of ROS by producing the NADPH required for regeneration of reduced glutathione, a potent endogenous antioxidant. Oxidative stress is an important factor in the etiology of a number of hepatic injuries, including nonalcoholic steatohepatitis (NASH) and hepatocarcinogenesis. In the latter, the frequency of mutations in thyroid hormone receptors (TRs) supports the concept that thyroid hormone acts as a tumor suppressor by reducing oxidative stress. This paper reviews the substrate cycles involved in this process. It also describes other mechanisms that permit rapid availability of T3 to cells undergoing oxidative stress.     

Ontogeny of maternal behavior in the laboratory rat: factors underlying changes in responsiveness from 30 to 90 days.

Male and female rats that were nonhandled or that were handled from weaning, and that had intact or impaired olfaction (intranasal zinc sulfate), were sensitized through continuous pup exposure commencing at 30, 45, 60, or 90 days of age. Nonhandled males and females were alike in latencies to become maternal at Day 30 but thereafter latencies of females became shorter and latencies of males lengthened; by 90 days males had markedly longer latencies than females and only 1/3 became maternal. Handling facilitated sensitization at 30 days among males and females but only among males at 45 and 60 days. Intranasal zinc sulfate reduced latencies of both males and females at all ages tested, but appeared most effective after 45 days of age. Gender differences in latencies persisted in adult animals even after combined treatments. Results indicate that both timidity and olfaction inhibit the onset of maternal responses to pups in virgin males and females, but they differ in relative importance by age and gender.     

The age-related pathomorphology of the thyroid in inhabitants of the European North

Thyroids of 185 males of different ages (from 17 to 75 years) were examined by histological and stereological methods. All persons died accidentally. Cases were not connected with endocrinological diseases. Maximum weight of organ (18.1 +/- 1.2 g) was at the age of 31-40 years. In all cases the thyroids were characterised by the large-follicular type of structure with a moderately pronounced colloid resorption and desquamation of thyrocytes. Statistically significant changes of nuclear volume and volume density of thyrocytes with age were found stereologically. It is concluded that the conditions of the European North influence the speed of the involutionary changes in the thyroid.     

Comparison of thyroid stimulating hormone and triiodothyronine response to thyrotrophin releasing hormone in the assessment of thyroid status.

The response to an intravenous dose of 200 microng of thyrotrophin releasing hormone (TRH) has been studied by estimating, by radioimmunoassay, baseline levels followed by further estimations of thyroid stimulating hormone (TSH) 20 minutes after the injection and triiodothyronine (T3) three hours after the injection in 112 patients referred for routine thyroid assessment. Comparison of diagnostic accuracy of the response to TRH gave similar results with both procedures but slightly better overall accuracy for the response measured by TSH assay. However, estimation of baseline T3 is a valuable test for hyperthyroidism, in contrast to baseline TSH, and combined with the estimation of T3 three hours after TRH injection provides an accurate additional test in borderline cases.     

The role of epigenetics in aging and age-related diseases

The role of epigenetics in aging and age-related diseases is a key issue in molecular physiology and medicine because certain epigenetic factors are thought to mediate, at least in part, the relationship between the genome and the environment. An active role for epigenetics in aging must meet two prior conditions: there must be specific epigenetic changes during aging and they must be functionally associated with the aged phenotype. Assuming that specific epigenetic modifications can have a direct functional outcome in aging, it is also essential to establish whether they depend on genetic, environmental or stochastic factors, and if they can be transmitted from one generation to the next. Here we discuss current knowledge about these matters and future directions in the field.     

Physiological relevance of thyroid stimulating hormone and thyroid stimulating hormone receptor in tissues other than the thyroid

Decades of research have provided strong evidence for a reciprocal relationship between the immune system and hormones of the hypothalamus-pituitary-thyroid (HPT) axis. Thyroid stimulating hormone (TSH), in particular, has been shown to have a variety of immune-regulating cytokine-like activities that can influence the outcome of T cell development in the thymus and intestine, and can affect the magnitude of antibody and cell-mediated responses of peripheral lymphocytes. Production of TSH and the expression of the TSH receptor are widely but selectively distributed across many different types of hematopoietic cells in the bone marrow, as well as among subsets of dendritic cells, monocytes and lymphocytes in the spleen and lymph nodes. In addition to their role in immunity, the involvement of TSH-producing hematopoietic cells in the microregulation of thyroid hormone activity represents a novel and potentially important aspect of the TSH-mediated immune-endocrine circuit.     

The role of age-related and adaptive changes in the vascular wall in atherogenesis in light of the theory of Academician I. V. Davydovski? on atherosclerosis

Aorta and coronary arteries (1053 and 386 cases, respectively) were evaluated in young persons. It is shown that atherosclerotic developments in the vessels are largely determined by hyperplastic involvement of the intima due to age-related vascular rearrangement and the hemodynamic factor. For aorta, these are represented by rhythmic structures which seem to give rise to the majority of the fibrous plaques. The findings are in consistence with I. V. Davydovsky's conceptions on age-related and adaptation changes in the vascular wall emerging during various human vital activities and supposed to underlie the development of atherosclerosis.     

Peroxides and peroxide-degrading enzymes in the thyroid

Iodination of thyroglobulin is the key step of thyroid hormone biosynthesis. It is catalyzed by thyroid peroxidase and occurs within the follicular space at the apical plasma membrane. Hydrogen peroxide produced by thyrocytes as an oxidant for iodide may compromise cellular and genomic integrity of the surrounding cells, unless these are sufficiently protected by peroxidases. Thus, peroxidases play two opposing roles in thyroid biology. Both aspects of peroxide biology in the thyroid are separated in space and time and respond to the different physiological states of the thyrocytes. Redox-protective peroxidases in the thyroid are peroxiredoxins, glutathione peroxidases, and catalase. Glutathione peroxidases are selenoenzymes, whereas selenium-independent peroxiredoxins are functionally linked to the selenoenzymes of the thioredoxin reductase family through their thioredoxin cofactors. Thus, selenium impacts directly and indirectly on protective enzymes in the thyroid, a link that has been supported by animal experiments and clinical observations. In view of this relationship, it is remarkable that rather little is known about selenoprotein expression and their potential functional roles in the thyroid. Moreover, selenium-dependent and -independent peroxidases have rarely been examined in the same studies. Therefore, we review the relevant literature and present expression data of both selenium-dependent and -independent peroxidases in the murine thyroid.