Hormone,vitamin and contaminant status during the moulting/fasting period in ringed seals (Pusa [Phoca] hispida) from Svalbard

This study investigates the potential effects of moulting, and the concomitant period of fasting undertaken by ringed seals, on hormone, vitamin and contaminant status in adult animals in a population from Svalbard, Norway, which has relatively low contaminant levels. Concentrations of circulating total and free thyroxine and triiodothyronine, circulating and hepatic vitamin A, hepatic persistent organic pollutants and their circulating hydroxyl metabolites were higher in moulting seals compared to pre-moulting seals. The opposite trend was observed for body condition, circulating calcitriol levels and hepatic mRNA expression of thyroid hormone receptor β. No differences were observed for circulating or hepatic vitamin E levels or hepatic mRNA expressions for deioidinase 1 or 2, or retinoic acid receptor α between the two seal groups. The observed differences are likely the result of increased metabolic rates required during moulting to maintain thermal balance and replace the pelage, in combination with mobilization of lipid soluble compounds from blubber stores during the fasting period that is associated with moulting. The present study shows that contaminant levels and their relationships with physiological or endogenous variables can be highly confounded by moulting/fasting status. Thus, moulting status and body condition should be taken into consideration when using variables related to thyroid, calcium or vitamin A homeostasis as biomarkers for contaminant effects.     

The influence of hypo- and hyperthyreosis on insulin receptors and metabolism

Changes in thyroid status affect metabolism not only directly, but influence it also by alterations in insulin secretion and action. Despite several investigations, these effects are, however, poorly characterised or even controversial. The aim of the studies was to investigate the effect of hyperthyreosis (HT) and hypothyreosis (HPT) on insulin binding by rat liver membranes. Some metabolic parameters reflecting insulin and thyroid hormones action were also determined. HT and HPT were developed by daily administration for 3 weeks of thyroxine (T (4) ) and thiouracil (TU), respectively. Experimental hyperthyreosis and hypothyreosis caused deep changes in metabolism. The greatest alterations were observed in body and thyroid glands weight, blood triiodothyronine (T (3) ), T (4), glucose, and insulin levels, liver glycogen amount and number of insulin receptors. HT reflected in rats in slower rate of growth and in smaller thyroid glands weight. In comparison to controls, T (4) concentration in HT was almost doubled and it was reduced by about 30% in HPT. Also, T(3), insulin and glucose levels in HT were heightened. Simultaneously, binding of insulin to liver membranes was elevated in HT and reduced in HPT. In HT the number of high affinity insulin receptors (HAIRs) and low affinity insulin receptors (LAIRs) was increased, whereas in HPT the amount of HAIRs was diminished. HT caused a drastic reduction of glycogen concentration in liver, but no changes were observed for muscle glycogen. Considering lipid metabolism, only free fatty acids (FFA) level in blood was changed (in HPT), but no differences were observed in serum concentration of triglycerides and cholesterol. Several metabolic changes observed in HT and HPT seem to be the dire ct consequence of alterations of thyroid hormone concentrations. These disturbances, together with the direct effect of HT or HPT on insulin secretion, binding and action lead, in turn, to changes in the other metabolic parameters. As a result of these disturbances the adaptive mechanisms appear. One of them is change in the number of insulin membrane receptors taking place even against the well known "down-regulation" theory.     

The effects of ACTH and dexamethasone upon plasma thyroid hormone levels and heat production in the domestic fowl

Treatment with long acting ACTH (20 IU kg-1) produces a large and sustained elevation of plasma corticosterone in the domestic fowl. Both ACTH treatment and administration of dexamethasone produce significant reductions in plasma concentrations of T4 and T3, and these changes are accompanied by a sustained hyperglycaemia. Despite the changes in circulating thyroid hormones only a small reduction in heat production (-14%) was induced by either treatment and mainly during the dark period. Whilst there may be some causal relationship between increased corticosterone secretion, decreased plasma thyroid hormone levels and reduced metabolic heat production it is unlikely that these responses alone account for the adjustments in energy expenditure observed in short term food deprivation.     

Further studies on the effect of diet on serum thyroid hormone concentrations and thyroid histology in rainbow trout,Salmo gairdneri (Pisces,Salmonidae)

Synopsis In a 3 × 2 factorial experiment examining the effects of combinations of ambient temperature (18°, 15°, 9° C) and dietary protein content (35% and 45%) on thyroid activity inSalmo gairdneri, although there was an apparent increase in activity of the thyroid in cold-adapted trout, assessed by histological appearance of the gland, there were no significant changes in serum thyroid hormone titers. In a second experiment examining the effects of combinations of ambient temperature (15°, 12.5°, 10°C) with dietary lipid content (6% and 16%) there was a similar apparent increase in thyroid activity in cold-adapted fish which was accompanied, in fish fed the higher lipid diet, with an increase in serum thyroxine (T4) and triiodothyronine (T3) levels. Trout fed an ascorbic acid-free diet (experiment 3) had lower serum T3 levels than in those given an ascorbic acid supplemented diet (1280 mg·kg^-1). In experiments 2 and 3 serum thyroid hormone concentrations were approximately inversely proportional to ambient temperature and concomitant weight gain, but no such correlation was evident in experiment 1 suggesting that the changes in hormone levels in experiments 2 and 3 were not ipso facto related to differences in either ambient temperature or weight gain but rather to the specific metabolic changes imposed by the dietary lipids or ascorbic acid deficiency.     

Circulating thyroid hormone levels and iodothyronine deiodinase activities in Nile tilapia (Oreochromis niloticus) following dietary exposure to Endosulfan and Aroclor 1254

We evaluated the effects of two organochlorinated environmental contaminants, Endosulfan and Aroclor 1254 on peripheral thyroid hormone metabolism and thyroid hormone plasma levels in Nile tilapia (Oreochromis niloticus). Tilapia were exposed through diet to 0.1 and 0.5 microg g(-1) of Endosulfan and 0.5 microg g(-1) of Aroclor 1254 for 21 and 35 days. Decreased plasma T4 and rT3 levels were observed in tilapia exposed to the lower dose of Endosulfan, while treatment with a higher dose and Aroclor 1254 produced no changes. Plasma T3 levels were not affected by these compounds. Hepatic type I deiodinase (D1) activity was depressed by a lower dose of Endosulfan and hepatic type III (D3) activity was increased following 35 days of exposure to the lower dose of Endosulfan and following 21 and 35 days of exposure to Aroclor 1254; while type II (D2) remained unchanged in liver as well as in all other organs analysed. Apart from hepatic D3 activity, Endosulfan and Aroclor 1254 also increased D3 activity in gill, but not in other tested organs. It is concluded that dietary exposure of tilapia to Endosulfan or Aroclor 1254 can lead to changes in circulating thyroid hormone levels and/or in peripheral thyroid hormone metabolism. The changes in hormone metabolism differ between tissues, eventually reflecting tissue-specific differences in adaptation.     

Circulating chemokines in patients with autoimmune thyroid diseases.

Chemokines are a group of small proteins that recruit different leukocyte subtypes to sites of inflammation and play important roles in initiating and maintaining immunological responses in autoimmune endocrine diseases including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies have found increased gene and protein expression of different kinds of chemokines not only within the thyroid gland but also within thyroid cells in GD or HT patients. A few studies have determined serum levels of chemokines, with conflicting results. We measured circulating concentrations of CCL2, CCL5, CXCL9, and CXCL10 in patients with GD, HT, and nontoxic nodular thyroid disease (NNT). While CCL2 and CXCL9 concentrations were comparable in patients with either AITD or NNT, CCL5 was significantly increased in GD patients compared with HT or NNT subjects. In contrast, CXCL10 levels were lower in patients with GD, but the difference was statistically significant only when compared with patients with HT (p=0.0018). Importantly, GD patients who relapsed or went into remission had significantly different levels of CXCL9 (p=0.0252). Serum levels of CCL2, CCL5, CXCL9, and CXCL10 did not reveal any correlation with thyroid volume; with the levels of thyrotropin (TSH), FT3, or FT4; or with the titers of TSH receptor antibody and thyroperoxidase antibody. These data suggest that the expression patterns of chemokines in various thyroid diseases differ from each other, which may reflect the distinct immune responses in HT and GD.     

The effects of selenium depletion and repletion on the metabolism of thyroid hormones in the rat

Rats were fed selenium-deficient (less than 0.005 mg selenium/kg) or selenium-supplemented diets (0.1 mg selenium/kg, as Na2SeO2) for up to five wks from weaning to assess the effects of developing selenium deficiency on the metabolism of thyroid hormones. Within two wks 3:5,3'-triiodothyronine (T3) production from thyroxine (T4) in liver homogenates from selenium-deficient rats was significantly lower compared with the activity in liver homogenates from selenium-supplemented rats. This decreased activity was probably responsible, in part, for the higher T4 and lower T3 concentrations in plasma from the selenium-deficient rats after 3, 4, and 5 weeks of experiment. Repletion of selenium-deficient rats with single intra-peritoneal injections of 200 micrograms selenium/kg body wt. (as Na2SeO3) 5 days before sampling reversed the effects of the deficiency on thyroid hormone metabolism and significantly increased liver and plasma glutathione peroxidase activities. However a dose of 10 micrograms selenium/kg body wt given to rats of similar low selenium status had no effect on thyroid hormone metabolism or glutathione peroxidase activity but did reverse the increase in hepatic glutathione S-transferase activity characteristic of severe selenium deficiency. Imbalances in thyroid hormone metabolism are an early consequence of selenium deficiency and are probably not related to changes in hepatic xenobiotic metabolizing enzymes associated with severe deficiency.     

The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.     

Thyroid homeostasis as studied by computer simulation

Physico-chemical factors alone may account for much of the thyroid gland homeostasis and by inference for homeostasis of basal energy metabolism in mammals. Computer simulations indicate that changes of several of the important rate constants for thyroid function have little effect on circulating thyroid hormone concentrations. This was especially true of the rate constants for thyroid hormone release from the thyroid gland and to a lesser extent of the rate constants governing thyroid hormone metabolism and excretion. The rate at which thyroid hormone levels in blood respond to changes was rather slow indicating that transient changes in dietary iodine or in the rate constants governing thyroid function would have little effect. If changes taking place over several days, such as during the initiation of lactation, the parameters of thyroid function change at a corresponding rate.     

Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases

Ceruloplasmin (Cp) is a ferroxidase involved in iron metabolism by converting Fe(2+) to Fe(3+), and by regulating cellular iron efflux. In the ceruloplasmin knockout (CpKO) mouse, the deregulation of iron metabolism results in moderate liver and spleen hemosiderosis, but the impact of Cp deficiency on brain neurochemistry and behavior in this animal model is unknown. We found that in contrast to peripheral tissues, iron levels in the hippocampus are significantly reduced in CpKO mice. Although it does not cause any discernable deficits in motor function or learning and memory, Cp deficiency results in heightened anxiety-like behavior in the open field and elevated plus maze tests. This anxiety phenotype is associated with elevated levels of plasma corticosterone. Previous studies provided evidence that anxiety disorders and long-standing stress are associated with reductions in levels of serotonin (5HT) and brain-derived neurotrophic factor (BDNF) in the hippocampus. We found that levels of 5HT and norepinephrine (NE), and the expression of BDNF and its receptor trkB, are significantly reduced in the hippocampus of CpKO mice. Thus, Cp deficiency causes an anxiety phenotype by a mechanism that involves decreased levels of iron, 5HT, NE, and BDNF in the hippocampus.     

Premature induction of glucokinase in the neonatal rat by thyroid hormone.

1. It was shown that the development of liver glucokinase in the rat coincided with a peak in the levels of circulating thyroid hormone at about the 16th postnatal day. 2. Administration of thyroid inhibitors blocked the development of the enzyme and administration of thyroid hormone restored activity to normal levels. 3. Glucokinase could be induced prematurely as early as the 2nd postnatal day by the administration of thyroid hormone followed by daily injection of glucose (10 mg/g body weight). 4. Glucocorticoids and corticotropin failed to induce glucokinase activity prematurely. 5. The postnatal increase in circulating thyroid hormone levels together with increased intake of carbohydrate at weaning may be the normal physiological stimulus for induction of this enzyme.     

Similar triiodothyronine releasing activity of thyroid stimulating antibodies in human and porcine thyroid slices

In an approach to addressing species specificity of thyroid stimulating antibodies (TSAb) stimulation of T3 release by Graves' sera was comparatively studied in human and porcine thyroid slices. A high sensitivity and specificity was found for the T3 bioassay independently on the use of human or porcine thyroid. Moreover, activity indices of the individual sera in both tissues were significantly correlated to each other and to circulating hormone levels in untreated disease. In conclusion, we suppose a lack of functionally relevant differences between target antigens, brought about probably by the TSH receptor itself and other membrane components, in human and porcine thyroid. Thus, for clinically applicable T3 releasing bioassay porcine thyroid may be alternatively used. In addition, this bioassay renders the advantage of reflecting the activity of disease.     

The impact of exercise on thyroid hormone metabolism in children and adolescents.

Thyroid hormones are important regulators of energy metabolism and may influence energy processes during physical exercise. There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents. Although some studies demonstrate a transient change in thyroid hormones during intense physical performance, most studies agree that these changes are of minor impact, practically reflecting the relative negative energy balance during strenuous exercise. This state of hypometabolism during intense physical performance has also been confirmed in highly trained female young athletes, who may be also characterized by reproductive axis dysfunction, manifested either as luteal-phase deficiency or amenorrhea, alongside the typical constellation of low T3, insulin and leptin levels. More importantly, strenuous exercise during childhood or adolescence is mostly accompanied by a delay of skeletal maturation, and height and may have a long-lasting negative effect on growth and acquisition of maximum bone mass. In conclusion, although thyroid hormones are only transiently or insignificantly changed during strenuous exercise, adequate caloric intake should be guaranteed in highly performing young athletes in order to counteract the relative negative energy balance and prevent alterations in endocrine-metabolic profile. Moreover, when growth and pubertal progression in very young athletes are significantly impaired, a reduction in the intensity of the physical exercise should be advocated in order to guarantee better final height and adequate acquisition of bone mass.     

Brain biogenic amines and altered thyroid function.

Evidence has been presented that alterations in thyroidal status produce marked changes in the metabolism of several biogenic amines in developing brain. Neonatal hypothyroidism induced either by ¹³¹I or by an anti-thyroid agent, methimazole, markedly decreased the concentrations of norepinephrine, dopamine and 5-hydroxytryptamine and the activity of their rate-limiting enzymes, tyrosine hydroxylase and tryptophan hydroxylase. However, the levels of 5-hydroxyindoleacetic acid, the chief metabolite of 5-hydroxytryptamine were elevated in several regions of the brain. Whereas thyroid deficiency in early life produced no appreciable change in whole brain monoamine oxidase activity, it was increased in mid brain and decreased in the hypothalamus. Brain acetylcholine levels were significantly elevated and the activity of acetylcholinesterase remained unchanged in rats made hypothyroid at 1 day of age. Delaying thyroidectomy for 20 days after birth produced less appreciable changes in norepinephrine and 5-hydroxytryptamine metabolism. Thyroid deficiency suppressed the ontogenesis of behavioural arousal and spontaneous locomotor activity. The administration of L-triiodothyronine to hypothyroid animals in early life restored the metabolism of various neurohumors virtually to the normal limits. However, when the replacement therapy was postponed until adulthood, L-triiodothyronine failed to produce any restorative effects, suggesting that a critical period exists in early life during which thyroid hormone must be present to permit normal developmental pattern of central amines. Data also have been obtained demonstrating that neonatal hyperthyroidism induced by daily administration of L-triiodothyronine results in an increased turnover of norepinephrine and 5-hydroxytryptamine. These amine changes were accompanied by a marked rise in the spontaneous locomotor activity in hyperthyroid rats. Finally, chronic treatment with lithium, an antimanic drug, also known to suppress thyroid hormone production, significantly decreased not only the spontaneous locomotor activity, but also changes in the turnover of 5-hydroxytryptamine and norepinephrine in neonatally hyperthyroid rats.     

Grades of Hypothyroidism

Seventy-nine patients with hypothyroidism and autoimmune thyroid disease were studied, and allotted to one of four categories on the basis of clinical and biochemical features. Firstly, patients with overt hypothyroidism had obvious clinical features of hypothyroidism and abnormal results from routine tests of thyroid function. Secondly, those with mild hypothyroidism, however, had minor and non-specific symptoms, but the routine measurements of circulating thyroid hormone concentration generally lay within the normal range, although they were significantly lower than those seen in subclinical hypothyroidism or in normal subjects. The serum concentration of thyroid-stimulating hormone (TSH) was raised in this group and their symptoms resolve with treatment. Thirdly, patients with subclinical hypothyroidism were asymptomatic, had a raised serum TSH concentration, but all other measurements of thyroid function are indistinguishable from those recorded in people with autoimmune thyroid disease without disturbance of thyroid function and in normal subjects. Lastly, subjects with circulating thyroid antibodies, normal indices of thyroid function, and a normal serum TSH concentration were indistinguishable biochemically from normal subjects.Thus hypothyroidism is a graded phenomenon, the most valuable features for defining the individual grade being the clinical manifestations, the serum TSH concentration, and the presence of circulating antibodies to thyroid tissue.     

Temporal sequence of neuroendocrine events associated with the transfer of male golden hamsters from a stimulatory to a nonstimulatory photoperiod

The transfer of male golden hamsters from long day (LD) to short day (SD) conditions results in gonadal atrophy within 8 weeks and significant reductions in LH, FSH, and prolactin (Prl) secretion as early as 4 weeks. Changes in hypothalamic neurotransmitter metabolism precede these changes in pituitary hormone secretion. Thus median eminence norepinephrine (NE) turnover declines steadily after SD exposure, although the differences as compared to turnover in LD hamsters are not significant until Week 4. Median eminence dopamine (DA) turnover is reduced significantly within 1 week. Turnover of NE and DA in the medial basal hypothalamus also changes significantly within 1 or 2 weeks of SD exposure, but the changes are not maintained through Week 8, despite continued reductions in levels of circulating LH, FSH, and Prl. Reductions in median eminence NE metabolism appear to be responsible for the decrease in LH and FSH release. Initial decreases in Prl release appear to be hypothalamic in origin, but the hypothalamic factor(s) responsible for this change is not evident. An increase in inhibitory input from tuberoinfundibular dopaminergic neurons is clearly not involved.     

Thyroid hormone status of Atlantic croaker exposed to Aroclor 1254 and selected PCB congeners

Atlantic croaker (Micropogonias undulatus) were exposed to the polychlorinated biphenyl (PCB) mixture (Aroclor 1254) or one of three individual congeners (planar PCB 77 or ortho-substituted PCB 47 and PCB 153) in the diet for 30 days to investigate the effects of PCBs on circulating thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Aroclor 1254 (0.2 and 1.0 mg/kg body mass/day) decreased plasma T3 levels consistently, but the effects on T4 levels were inconsistent from year to year. Exposure to PCB 153 (0.1 and 1.0 mg/kg body mass/day) significantly lowered both T4 and T3, while PCB 47 at the same doses had no effect on thyroid hormone levels. The lower doses of PCB 77 (0.004, 0.01 and 0.02 mg/kg body mass/day) had no effect on T4 or T3, whereas the highest dose (0.1 mg/kg body mass/day) increased T4 levels significantly. The results of the present study demonstrate that exposure to PCBs at environmentally realistic concentrations can have profound effects on the thyroid status of Atlantic croaker. The ortho-substituted PCB 153 appears to contribute at least partially to the deleterious effects of Aroclor 1254 on thyroid status, whereas the planar PCB 77 at concentrations present in the mixture is unlikely to alter thyroid hormone levels.