Selenium,zinc, and thyroid hormones in healthy subjects

Iodothyronine 5′ deiodinase, which is mainly responsible for peripheral T₃ production, has recently been demonstrated to be a selenium (Se)-containing enzyme. The structure of nuclear thyroid hormone receptors contains Zinc (Zn) ions, crucial for the functional properties of the protein. In the elderly, reduced peripheral conversion of T₄ to T₃ with a lower T₃/T₄ ratio and overt hypothyroidism are frequently observed. We measured serum Se and RBC GSH-Px (as indices of Se status), circulating and RBC Zinc (as indices of Zn status), thyroid hormones and TSH in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid under- or malnutrition conditions, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. Low T₃/T₄ ratios and reduced Se and RBC GSH-Px activity were observed only in the older group. A highly significant linear correlation between the T₃/T₄ ratio and indices of Se status was observed in the older group of subjects (r=0.54;p<0.002, for Se;r=0.50;p<0.002, for RBC GSH-Px). Indices of Zn status did not correlate with thyroid hormones, but RBC Zn was decreased in older as compared with younger subjects. We concluded that reduced peripheral T₄ conversion is related to impaired Se status in the elderly.     

Elements in erythrocytes of population with different thyroid hormone status

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T₃, T₄, TSH, FT₃, and FT₄ detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T₃/T₄ ratio, and between Zn and TSH.     

Are thyroid hormones mediators of incubation temperature-induced phenotypes in birds?

Incubation temperature influences a suite of traits in avian offspring. However, the mechanisms underlying expression of these phenotypes are unknown. Given the importance of thyroid hormones in orchestrating developmental processes, we hypothesized that they may act as an upstream mechanism mediating the effects of temperature on hatchling phenotypic traits such as growth and thermoregulation. We found that plasma T₃, but not T₄ concentrations, differed among newly hatched wood ducks (Aix sponsa) from different embryonic incubation temperatures. T₄ at hatching correlated with time spent hatching, and T₃ correlated with hatchling body condition, tarsus length, time spent hatching and incubation period. In addition, the T₃ : T₄ ratio differed among incubation temperatures at hatch. Our findings are consistent with the hypothesis that incubation temperature modulates plasma thyroid hormones which in turn influences multiple aspects of duckling phenotype.     

Diurnal rhythms of plasma growth hormone,somatostatin, thyroid hormones,cortisol and glucose concentrations in rainbow trout,Oncorhynchus mykiss,during progressive food deprivation

Abstract

The diurnal patterns of changes in plasma cortisol, growth hormone (GH), somatostatin‐14 (SRIF), thyroid hormones (L‐thyroxine, T₄ and triiodo‐L‐thyronine, T₃) and glucose were investigated in rainbow trout, Oncorhynchus mykiss, both during single meal‐feeding and during a progressive fast of 13 weeks. All measured variables exhibited a diurnal pattern in fed rainbow trout, most of which appeared to be correlated with the time of feeding (30–60 min after the onset of light), while additional changes, associated with the scotophase were also found for cortisol. Although fasting had no affect on mean daily plasma cortisol or SRIF concentrations, there was a progressive increase in mean daily plasma GH concentrations and a progressive decrease in mean daily plasma thyroid hormone and glucose concentrations associated with fasting. However, for GH, significant changes were not evident until week 10 of the fast. In addition, fasting appeared to phase‐shift the diurnal patterns of plasma GH, cortisol and glucose concentrations; the consequence of such a shift is that conclusions as to the effects of fasting, if based on a single time of sampling, may be flawed.     

Inverse relationship between diurnal rhythms in plasma levels of thyroid hormones and pineal arylalkylamine-N-acetyltransferase (AANAT) activity in an air-breathing fish,Clarias gariepinus

Plasma levels of thyroid hormones (T₄ and T₃) and pineal AANAT activity exhibited prominent diurnal rhythms during all the four phases (quiescent, progressive, breeding, and regressive) of the fish, Clarias gariepinus. During all the four phases, we observed that (i) the acrophase (peak) of the circadian rhythm of both T₃ and T₄ occurred around midday, while the acrophase of AANAT activity rhythm was recorded during midnight, (ii) a significant negative correlation existed between plasma levels of the thyroid hormones and AANAT activity, and (iii) a direct relationship existed between water temperature/daylength and plasma levels of thyroid hormones, and an inverse relationship between water temperature/daylength and AANAT activity. On the basis of these findings, we conclude that an inverse relationship exists between the diurnal rhythms in plasma levels of thyroid hormones and pineal AANAT activity. The observed inverse relationship between the levels of thyroid hormones and pineal AANAT activity seems to be maintained by seasonal changes in water temperature and daylength.     

Changes in whole body concentrations of thyroid hormones and cortisol in metamorphosing conger eel

Summary To clarify the hormonal regulation of metamorphosis of the conger eel (Conger myriaster), changes in whole body concentrations of thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), and cortisol during metamorphosis were examined, as well as the changes in the histological activity of the thyroid gland. In larvae before metamorphosis, T₄ and T₃ levels were less than 5 and 0.15 ng·g^-1 respectively. Levels of T₄ increased to about 30 ng·g^-1 during early metamorphosis, and decreased subsequently. Levels of T₃ increased gradually in early metamorphosis, and then increased abruptly to about 2.0 ng·g^-1 in late metamorphosis. Before metamorphosis, cortisol levels of the leptocephali less than 11 cm in total length were greater than 200 ng·g^-1. Cortisol levels decreased rapidly in larger premetamorphic leptocephali, and low levels were maintained throughout the metamorphic period. Histological observation revealed an activation of the thyroid gland in early metamorphosis; thyroid follicle epithelial cells became columnar and their nuclei larger. Active uptake of colloid by these cells and intensive vascularization of the gland were also observed. By the end of metamorphosis, follicle epithelial cells became squamous, indicating a low level of glandular activity. These results suggest that thyroid hormone plays an important role in regulation of conger eel metamorphosis.Abbreviations AL anal length - TL total length - T ₃ triiodothyronine - T ₄ thyroxine     

Post‐translational modifications of transthyretin affect the triiodonine‐binding potential

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys₁₀), which is frequently affected by oxidative post‐translational modifications. As Cys₁₀ is part of the thyroid hormone‐binding channel within the TTR molecule, PTM of Cys₁₀ may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys₁₀ modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype‐ and site‐specific manner with S‐glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function‐specific patterns of TTR with a substantial decrease in S‐sulphonated, S‐cysteinylglycinated and S‐glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys₁₀ seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability.     

Nongenomic signaling pathways triggered by thyroid hormones and their metabolite 3‐iodothyronamine on the cardiovascular system

Thyroid hormones play a wide range of important physiological activities in almost all organism. As changes in these hormones levels—observed in hypothyroidism and hyperthyroidism—promote serious derangements of the cardiovascular system, it is important to know their mechanisms of action. Although the classic genomic actions which are dependent on interaction with nuclear receptors to modulate cardiac myocytes genes expression, there is growing evidence about T₃ and T₄‐triggered nongenomic pathways, resulted from their binding to plasma membrane, cytoplasm, or mitocondrial receptors that leads to a rapidly regulation of cardiac functions. Interestingly both actions converge to amplify thyroid hormone effects on cardiovascular system. T₃ and T₄ nongenomic actions modify inotropic and chronotropic effects, cardiac action potential duration, cardiac growth, and myocyte shape by protein translation through protein kinases‐dependent signaling cascades, which include PKA, PKC, PI3K, and MAPK, and changes on ion channels and pumps activity. In respect to the decreased systemic vascular resistance seen in hyperthyroidism, T₃ appears to activate NOS or ATP‐sensitive K⁺ channels. In addition, a novel biologically active T₄‐derived metabolite has been described, 3‐iodothyronamine, T₁AM, which also acts through membrane receptors to mediate nongenomic cardiac effects. This metabolite influences the physiological manifestations of thyroid hormone actions by inducing opposite effects from those stimulated by T₃ and T₄, such as negative inotropic and chronotropic effects. Therefore, beyond genomic and nongenomic effects of thyroid hormones, it is crucial for there to be an equilibrium between T₃ or T₄ and T₁AM levels for maintaining cardiac homeostasis. J. Cell. Physiol. 226: 21–28, 2010. © 2010 Wiley‐Liss, Inc.     

Dynamics of Thyroid Hormones at Early Stages of Development of the Sturgeon Acipenser güldenstadti

Using radioimmunological method, the level and dynamics of thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃) were studied in eggs, embryos, and pre-larvae of the Russian sturgeon Acipenser güldenstadti L. The level of hormones in eggs was higher than in the individuals at the stage of hatching. In embryogenesis the content of T₄ and T₃ hormones changed simultaneously, while in pre-larvae, synchronization was absent. The maximal T₄ values in sturgeon pre-larvae were recorded not long before transition to active nutrition. The T₄ level was statistically significantly higher in eggs and larvae developed from the eggs with a high degree of fertility. The problem of participation of thyroid hormones in processes of development and formation of adaptive mechanisms in early ontogenesis of sturgeons is discussed.     

Induction of metamorphosis in the sand dollar Peronella japonica by thyroid hormones

The larva of the sand dollar Peronella japonica lacks a mouth and gut, and undergoes metamorphosis into a juvenile sand dollar without feeding. In the present study, it was found that thyroid hormones accelerate the metamorphosis of P. japonica larvae. The contents of thyroid hormones in larvae increased gradually during development. Thiourea and potassium perchlorate, inhibitors of thyroid hormone synthesis, delayed larval metamorphosis and simultaneously repressed an increase in the content of thyroxine in the larval body. These results suggest that the P. japonica larva has a system for synthesis of thyroid hormones that act as factors for inducing metamorphosis.     

Effect of selenium supplementation on thyroid hormone levels and selenoenzyme activities in growing lambs

The aim of the present study was to evaluate the effects of selenium supplementation on thyroid hormone metabolism and selenoenzyme activities in lambs. Twelve 20-d-old male lambs were assigned to one of two diets: A (0.11 ppm Se) and B (supplemented with 0.2 ppm selenium as sodium selenite). Blood samples were collected weekly for the determination of T₃, T₄, and selenium levels. The response to thyrotropin-releasing hormone (TRH) challenge was estimated at the 11th and 20th wk. Animals were slaughtered at wk 20 and tissues were collected for enzyme determination. Plasma selenium concentration was significantly higher in supplemented lambs (p<0.001). Plasma T₃ and T₄ levels remained similar in both groups. Type I deiodinase activity (ID-I) was decreased in the liver (p<0.05) and increased in the pituitary (p<0.01) of supplemented animals. No ID-I activity was detected in the thyroid. Pituitary type II deiodinase activity (ID-II) remained unchanged. The response to TRH challenge did not differ between the two groups for both challenges, but in group B, the second TRH challenge (20th wk) resulted in a significantly higher T₃ response compared to the first one (11th wk) (p<0.05). In conclusion, the lack of effects of Se supplementation on thyroid hormone metabolism demonstrates that enzyme activity is homeostatically controlled and selenium is incorporated in that order to ensure the maintenance of thyroid hormone homeostasis.     

Effects of Pinealectomy and Exogenous Melatonin on the Thyroid Gland Activity Varies in Relation to Reproductive Status of Male Spotted Munia (Lonchura punctulata; Aves,Passeriformes)

The purpose of this investigation was to explore whether the pineal organ and its hormone melatonin has any influence on the activity of thyroid glands, if so, how that relates to the reproductive status of a hitherto unstudied seasonally breeding wild bird. Accordingly, an identical experimental regimen was followed with adult male spotted munia (Lonchura punctulata; Passeriformes) during both its gametogenically active (August-September) and inactive (March-April) phases of the annual reproductive cycle. In either case, the levels of circulating thyroid hormones (both T₃ and T₄) and cellular characteristics of thyroid glands in groups of birds were studied following surgical removal of the pineal gland and/or daily afternoon administration of melatonin (10 μg/ 100 g body weight/ day for 30 days). The results of the same experimental schedule were found to be different depending on the sexual status of the concerned birds. During the breeding phase, pinealectomy (Px) induced significantly decreased values of T₃ and increased for T₄ along with hypertrophy of the thyroid follicular cells (TFC). The changes were reversed in melatonin treated Px birds. An increased amount of T₃ and decreased concentration of serum T₄ were also observed in melatonin injected intact birds. Conversely, the responses of TFC and of thyroid hormones in blood to either Px, or Px with melatonin, or to melatonin alone in intact munias during their inactive reproductive phase were just opposite to those noted during the breeding phase. The results of the present study suggest an influence of the pineal upon the thyroid in spotted munia. Moreover, it appears that this influence is carried out by melatonin, the action of which is reversible in relation with the gametogenic status of the concerned avian species.     

Further studies on the regulation of the Harderian glands of golden hamsters by the thyroid gland

Summary Long-term increased or decreased circulating levels of thyroid hormones significantly modify porphyrin concentrations and morphology in the Harderian glands of male and female hamsters. Administration of T₃ reduced porphyrin concentrations in females; this treatment or decreasing thyroid hormone levels with KClO₄ suppressed the post-castration rise of porphyrins in males. Hypophysectomy led to increased porphyrins in the Harderian glands of males; this rise was suppressed in hypophysectomized males by T₃ or T₄. In females, hypophysectomy reduced porphyrins which were further reduced by daily administration of T₃ or T₄. These modifications in the normal females were identical in castrated males. Mitotic activity in the Harderian glands of females was stimulated by KClO₄ and by hypophysectomy with or without exogenous T₃. In males, castration increased mitotic activity which was suppressed by T₃ and exacerbated by KClO₄. Increased mitotic activity seemingly follows loss of tissue mass. The data show that thyroid hormones act directly on the Harderian glands rather than indirectly through modification of TSH synthesis/release. Female type glands in males are a consequence of loss of gonadal androgens by castration, or by suppression or loss of thyroid hormones by hypophysectomy or by treatment with KClO₄. However, male type glands in females are the result of androgen treatment, and/or increased levels of thyroid hormones via reduced ambient temperatures or of photic input. We conclude that regulation of the Harderian gland appears to be different in the two sexes.Abbreviations T ₃ Triiodothyronine - T ₄ Thyroxine - TSH Thyroid Stimulating Hormone - KClO ₄ Potassium Perchlorate - h hours - ml milliliter - mg milligram - g gram - male - female - castrated male - AP hypophysectomized - CON Control - ALA delta aminole-vulenic acid - HG Harderian Gland     

Reproductive and thyroid hormone profiles in captive Western fence lizards (Sceloporus occidentalis) after a period of brumation

Seasonal fluctuation in serum concentrations of sex steroid (testosterone [T] and 17β‐estradiol [E₂]) and thyroid (triiodothyronine [T₃] and thyroxine [T₄]) hormones was determined in captive Western fence lizards (Sceloporus occidentalis). Samples were collected from male and female breeding pairs weekly for a 4‐month period after their emergence from artificial brumation. Circulating levels of E₂ corresponded with the expected vitellogenic and ovulatory cycles in females, and surprisingly, E₂ in males followed a similar pattern, indicating a possible role in breeding behavior. Serum T was elevated in male lizards for the first 6 weeks after emergence from brumation, possibly related to an increase in the onset of active spermatogenesis. Thyroid hormones showed little cyclical activity throughout the breeding period, with the exception of small increases of T₃ at weeks 8 and 16, possibly implying an active role of this hormone with ovulation in females. Overall, these baseline hormone data are not only useful in developing this animal as a laboratory reptile model for assessment of endocrine‐mediated toxicity, but also of value for understanding herpetological endocrinology and for application in the conservation of threatened species. Zoo Biol 27:36–48, 2008. © 2007 Wiley‐Liss, Inc.     

Thyroid hormones increase liver and muscle thermogenic capacity in the little buntings (Emberiza pusilla)

Thyroid hormones can increase energy expenditure and stimulate basal thermogenesis by lowering metabolic efficiency. In the present study, we examined the effects of thyroid hormones on basal heat production as well as on several physiological and biochemical measures indicative of thermogenic capacity to test our hypothesis that thyroid hormones stimulate increases in thermogenesis in little buntings. Little buntings that fed on thyroxine (T₄)–laced poultry food of 3 and 5 ppm concentrations showed increases in basal metabolic rate (BMR) during the 3-week acclimation. At the end, these buntings had lower body weights, higher levels of contents of mitochondrial protein, state 4 respiration and cytochrome c oxidase activity in liver and muscle, and higher concentrations of serum triiodothyronine (T₃) and T₄ compared to control buntings. These results support the argument that thyroid hormones play an important role in the regulation of thermogenic ability in buntings by stimulating mitochondrial respiration and enzyme activities associated with aerobic metabolism.     

Metabolism of glucose and glutamine in lymphocytes from graves' hyperthyroid patients: influence of methimazole treatment

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentiation of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macrophages and their effects seem to occur mainly through the Krebs cycle. Alterations in the hexokinase, citrate synthase, glucose-6-phosphate dehydrogenase and glutaminase activities in lymphocytes from patients with Graves' disease, either untreated or on methimazole (MMI) therapy were investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24 h in the presence of MMI, T₃ and T₄ using concentrations close to the physiological. Changes in the conversion of [U-¹⁴C]-glucose and [U-¹⁴C]-glutamine to ¹⁴CO₂ as caused by the addition of MMI, T₃ or T₄ to the culture medium were also evaluated. The results indicate that high levels of thyroid hormones might stimulate the metabolism of glucose and glutamine for a short period of time but, if the stimulus is maintained, the utilization of glutamine by lymphocytes is then suppressed. Moreover, MMI does affect lymphocyte metabolism but the significance of this finding for its immunosuppressive effect remains to be examined.     

Fast Screening of Whole Blood Samples and Pharmaceutical Compounds for Enantiorecognition of Free L‐T3, L‐T4, and D‐T4

A fast screening method of whole blood was proposed for enantiorecognition of free L‐T₃ , L‐T₄, and D‐T₄. Stochastic microsensors based on four inulins (IN, IQ, TEX, and HD) immobilized on diamond paste (DP) were used for recognition of free L‐T₃ , L‐T₄, and D‐T₄. For the enantiorecognition of free L‐T₄ and D‐T₄ in whole blood and pharmaceutical samples, the best microsensor was the one based on TEX/DP (wide linear concentration ranges, and low limits of quantification). The best limit of detection for the assay of free L‐T₃ (400 fmol/L) was recorded using the microsensors based on HD/DP, while for the assay of free L‐T4, and D‐T4 the best limit of determination (1 pmol/L) was recorded using the TX/DP‐based microsensor. For the enantiorecognition of free L‐T₃ in whole blood and pharmaceutical samples the best microsensor was the one based on HD/DP (the wider linear concentration range, and the lower limit of quantification – of pmol/L magnitude order). For the enantiorecognition of free L‐T₃ in whole blood and pharmaceutical samples the best microsensor was the one based on HD/DP (the wider linear concentration range, and the lower limit of quantification – of pmol/L magnitude order). Free L‐T₃ , L‐T₄, and D‐T₄ were recovered with high reliabilities in whole blood samples (recoveries higher than 99.00%, with RSD values lower than 1.00%) and pharmaceutical samples (recoveries higher than 95.00% with RSD values lower than 1.00%). Chirality 27:973–978, 2015. © 2015 Wiley Periodicals, Inc.     

The Influence of Human Growth Hormone (GH) and Thyroxine (T4) on the Differentiation of Adipose Tissue in the Fetus

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T₄ levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T₄ increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T₄ (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a “critical” or “sensitive” period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitmentheplication during this period. Furthermore, T₄ but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T₄ may have a major role in preadipocyte recruitmentheplication during late fetal life.     

Histo-morphology of the thyroid gland during the larval development of Pleurodema borellii (Anura,Leptodactylidae)

The thyroid gland is essential in anurans, since thyroid hormones (TH) are the main regulators of larval development. Its absence or inactivity interrupts development and precludes metamorphosis. Histological changes are important diagnostic criteria for evaluating thyroid gland activity. However, there is a large larval diversity where the development of the thyroid gland development has not been studied. Pleurodema borellii is an anuran from northwest of Argentina with typical omnivorous pond tadpoles that can be easily raised in captivity. This study explores the histo-morphological changes of the thyroid gland architecture during larval development. Histological parameters indicate peak glandular activity in parallel with the intensity of the metamorphic transformations. These parameters regress towards the end of metamorphosis, indicating low TH release. P. borellii's thyroid gland does not appear to have relevant activity in post-metamorphic juvenile stages. This study is a first step towards understanding endocrine regulation during the development of Pleurodema borellii, and a reference to future studies in this species involving thyroid-dependent processes.