Regulation Of Thyroid Function Research Articles

Management of hypo- and hyperthyroidism during pregnancy.

Pregnancy has profound effects on the regulation of thyroid function, and on thyroidal functional disorders, that need to be recognized, carefully assessed and correctly managed. Relative hypothyroxinemia and goitrogenesis may occur in healthy women who reside in areas with restricted iodine intake, strongly suggesting that pregnancy constitutes a stimulatory challenge for the thyroid. Overt thyroid dysfunction occurs in 1-2% of pregnant women, but mild forms of dysfunction (both hyper- and hypothyroidism) are probably more prevalent and frequently remain unrecognized. Alterations of maternal thyroid function have important implications for fetal and neonatal development. In recent years, particular attention has been drawn to the potential risks for the developing fetus due to maternal hypothyroxinemia during early gestation. Concerning hyperthyroidism, the two main causes of thyrotoxicosis in the pregnant state are Graves' disease and gestational transient thyrotoxicosis (GTT). The natural history of Graves' disease is altered during pregnancy, with a tendency for exacerbation during the first trimester, and amelioration during the second and third trimesters. The natural history of the disorder must be considered when treating patients, since antithyroid drugs cross the placenta and can directly affect fetal thyroid function. Algorithms to routinely screen pregnant women for thyroid dysfunction have been proposed in recent years, but these have not yet been implemented systematically, nor have they been the subject of cost-effectiveness analyses.

Urinary iodine concentration during pregnancy in an area of unstable dietary iodine intake in Switzerland.

We prospectively investigated urinary iodine concentration (UIC) in pregnant women and in female, non-pregnant controls in the canton of Berne, Switzerland, in 1992. Mean UIC of pregnant women [205 +/- 151 microg iodine/g creatinine (microg l/g Cr); no. = 153] steadily decreased from the first (236 +/- 180 microg l/g Cr; no. = 31) to the third trimester (183 +/- 111 microg l/g Cr, p < 0.0001; no. = 66) and differed significantly from that of the control group (91 +/- 37 microg l/g Cr, p < 0.0001; no. = 119). UIC increased 2.6-fold from levels indicating mild iodine deficiency in controls to the first trimester, demonstrating that high UIC during early gestation does not necessarily reflect a sufficient iodine supply to the overall population. Pregnancy is accompanied by important alterations in the regulation of thyroid function and iodine metabolism. Increased renal iodine clearance during pregnancy may explain increased UIC during early gestation, whereas increased thyroidal iodine clearance as well as the iodine shift from the maternal circulation to the growing fetal-placental unit, which both tend to lower the circulating serum levels of inorganic iodide, probably are the causes of the continuous decrease of UIC over the course of pregnancy. Mean UIC in our control group, as well as in one parallel and several consecutive investigations in the same region in the 1990s, was found to be below the actually recommended threshold, indicating a new tendency towards mild to moderate iodine deficiency. As salt is the main source of dietary iodine in Switzerland, its iodine concentration was therefore increased nationwide in 1998 for the fourth time, following increases in 1922, 1965 and 1980.

Regulation of Thyroid Function in Mice with Extracts of Emblica officinalis L. and Bauhinia purpurea L.

ABSTRACT The role of Emblica officinalis L. and Bauhinia purpurea L. extracts in regulating thyroid functions was studied in male mice. Oral administration of Emblica officinalis L. fruit extract at 30 mg/kg body weight (b.wt.) each day for 20 days decreased serum T3 and T4 concentrations and hepatic O2 consumption. In contrast, daily administration of Bauhinia purpurea at 2.5 mg/kg b. wt. each day for 20 days increased serum T4 concentration and O2 consumption. Both the plant extracts exhibited hepatoprotective effects as evidenced by decreased lipid per-oxidation. In animals treated with Emblica officinalis, activities of super-oxide dismutase and catalase remained unaffected, but a significant increase in both of these antioxidative enzymes was observed in Bauhinia purpurea treated animals, indicating that extract of Emblica officinalis, but not the extract of Bauhinia purpurea, may have direct free radical scavenging role.

Water and Ethanol Extracts of Piper nigrum in Regulating Thyroid Function and Lipid Peroxidation in Mice

An investigation was made to evaluate the effects of water and ethanol extracts of Piper nigrum L. fruits in the alteration of the serum thyroid hormone concentrations and tissue lipid peroxidation in liver, the main target organ of many drugs. The alcohol extract, at a dose of 4.0 mg/kg for 15 days, caused thyrotoxicosis as evidenced by increased concentrations of thyroxine and triiodothyronine. A concomitant increase in hepatic lipid peroxidation with a decrease in superoxide dismutase and/or catalase activities also indicated its peroxidative effect. However, a trial with the aqueous extract did not exhibit any toxic effect either on thyroid or in liver functions. Rather, the latter extract appeared to be antithyroidic and antiperoxidative in nature as it could decrease serum thyroid hormone concentrations and hepatic lipid peroxidation, respectively. It is suggested that the aqueous extract of Piper nigrum may be preferred over the alcohol extract for therapeutic uses.

Thyrotropin releasing hormone (TRH) in the hippocampus of Alzheimer patients.

Thyrotropin-releasing hormone (TRH) is best known for its hypothalamic neuroendocrine role in regulating thyroid function. In extra-hypothalamic regions in vitro, we have shown TRH to have a protective effect against synaptic loss and neuronal apoptosis. A role for TRH in Alzheimer's disease (AD) has not been established previously. In this study, we examined the content of the TRH peptide in the hippocampus of elderly controls (n=5) and AD patients (n=7) by radioimmunoassay (RIA). The TRH concentration was decreased in the AD hippocampus compared to normal elderly controls (p < 0.01). In a separate series of experiments utilizing primary cell cultures made from rat hippocampus, TRH peptide concentration was depleted by the addition of TRH antiserum. TRH withdrawal was found to enhance the activity of glycogen synthetase kinase-3 (GSK-3beta), a critical enzyme necessary for the phosphorylation of tau, as well as the phosphorylation of the tau protein itself. This TRH depletion induced upregulation in phosphorylation that was observed to initiate axonal retraction in cultured neurons. These data suggest that TRH within the hippocampus can regulate the activity of various proteins by phosphorylation/dephosphorylation that may be involved in the pathogenesis of AD.

Long-term effects of malnutrition during lactation on the thyroid function of offspring.

Some studies have shown that the mother's nutritional condition may influence offspring's endocrine function through metabolic imprinting. Recently, we showed that the kind of maternal malnutrition during lactation affects adult body weight of the offspring and it is related to milk composition. We studied lactating rats fed an 8 % protein-restricted diet (PR), a control 23 % protein diet (C), and an energy-restricted diet group (ER). After weaning, all animals received a normal diet until they were 180 days of age. At this time, the animals received a single i. p. injection of (131)I and were sacrificed 2 h after the injection. Total triiodothyronine (TT3) and total thyroxin (TT4) serum concentrations were measured by enzyme immunoassay. The PR group had significantly a higher thyroid (131)I uptake, TT3 serum concentration and in TT4 serum concentration, compared to the controls. The ER group had only significantly higher TT3 serum concentration. These results showed that thyroid function regulation in adulthood may depend on maternal nutritional condition during lactation. Probably, PR group had a high thyroid function, whereas the ER group only had an increase in the deiodination of T4. The hyperthyroidism in the PR group could explain the low body weight observed in those animals.

INTERLEUKIN 1β (IL-1β) ACTION IN PORCINE THYROID CELLS INVOLVES THE CERAMIDE SIGNALLING PATHWAY

Interleukin 1 beta (IL-1β) is often associated with thyroidal autoimmune diseases. This cytokine has been largely described to trigger an important biological signalling pathway: the sphingomyelin/ceramide pathway. In this report we show that IL-1β induces ceramide formation and sphingomyelin degradation in porcine thyroid cells via the activation of a neutral sphingomyelinase. Among the potential targets of IL-1β and ceramides action, we have investigated the role of an atypical protein kinase C (PKC), the PKC zeta. We show that both IL-1β and ceramides lead to an increase of PKCζ activity. All these results suggest an important role for ceramides and IL-1β in regulation of thyroid function, leading to cell survival or to apoptosis.

Morphological and biochemical changes in the thyroid gland of the lizard Podarcis sicula (Reptilia, Squamata) induced by VIP treatment

The effects of exogenous vasoactive intestinal polypeptide (VIP) involvement in the regulation of thyroid function were detected in the lizard Podarcis sicula. Variations in thyroid gland morphology, thyroid‐stimulating hormone (TSH), 3,5,3'‐triiodo‐L‐thyronine (T3) and L‐thyroxine (T4) plasma levels, were studied in this species after treatment with VIP, during winter and summer. The polypeptide had a stimulatory effect on thyroid hormone secretion throughout the year. Plasma T4 and T3 levels significantly increased; maximal values were reached in specimens exposed longer to treatment. No difference in plasma TSH levels was observed between control and treated specimens, indicating that, in P. sicula, the site of VIP action might be better identified at thyroidal rather than hypophyseal level. Consistently with these results, the morphology of the thyroid gland also appeared stimulated after treatment with VIP, showing an increase in thyroid‐cell height, numerous intracellular colloid droplets PAS‐positive, and enlarged blood vessels around the follicles.

Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring

The function of the thyroid gland is to produce the thyroid hormones T3 and T4, which regulate gene transcription throughout the body (1). In medical practice, the thyroid becomes an issue when its size or shape becomes abnormal or when it produces too much or too little hormone. Thus, we typically think of the thyroid with reference to the clinical states of goiter, or hyper- or hypothyroidism. But what is the physiology of the thyroid when the gland and the entire hypothalamic-pituitary-thyroid axis are intact? As first year medical students ask each year, Why exactly do we have a thyroid, at all?

Combined Effects of Ashwagandha, Guggulu and Bauhinia Extracts in the Regulation of Thyroid Function and on Lipid Peroxidation in Mice

The combined effects of three different plant extracts (Ashwagandha root, Guggulu gum and Bauhinia bark) on the regulation of thyroid function and on lipid peroxidation have been studied in laboratory mice. Daily administration of these extracts (1.4g kg−1 Ashwagandha, 0.2 g kg−1 Guggulu and 2.5g kg−1 Bauhinia) for 30 days enhanced serum concentrations of both thyroid hormones (thyroxine and triiodothyronine) without altering hepatic lipid peroxidation, indicating that these plant extracts, given in combination, stimulate thyroid function without hepatotoxic effects. The plant extracts also induced an increase in hepatic catalase activity, further suggesting the hepatoprotective nature of the extracts. These plant extracts might be used to formulate a drug for the treatment of hypothyroidism.

Effects of a Single Venous Dose of Zinc on Thyroid Status in Healthy Individuals and Patients With Graves′ Disease

Zinc metabolism may regulate thyroid function acting at TRH (thyrotropin-releasing hormone) synthesis, peripheral deiodination of T4 (tetraiodothyronine), and binding of thyroid hormones to nuclear receptors. The aim of this study was to investigate the effect of acute zinc administration on TSH (thyroid-stimulating hormone), FT3 (free triiodothyronine), and FT4 (free tetraiodothyronine) in 10 healthy individuals and 12 hyperthyroid patients with Graves' disease. All these individuals were studied following 25 mg Zn++ administered intravenously, at 7:00 a.m. after 12 h fast. Blood samples collected at 0, 3, 30, 60, 90, and 120 min after zinc administration showed no significant alteration in the plasma levels of TSH, FT3, and FT4 in hyperthyroid patients. There were no changes in the plasma levels of FT3 and FT4 in the control subjects, but TSH levels were acutely depressed by zinc administration. This study suggests that zinc given acutely and in pharmacological doses does not affect thyroid function in hyperthyroid subjects, but affect plasma TSH levels in healthy individuals.

In vivo and in vitro regulation of thyroid leukemia inhibitory factor (LIF): marker of hypothyroidism.

Several cytokines regulate thyroid function and may be involved in the pathogenesis of thyroid disorders, including euthyroid sick syndrome. Leukemia inhibitory factor (LIF), a neuroimmune pleiotropic cytokine, was measured to assess its role in hypothalamic-pituitary-thyroid function. Mean circulating serum LIF levels in 10 hypothyroid patients [TSH, 23+/-0.5 mIU/L (mean+/-SEM); free T4, 0.77+/-0.1 ng/dL] was 0.29+/-0.04 ng/mL, 145% higher (P < 0.04) than in 20 normal subjects (LIF, 0.20+/-0.02 ng/mL; TSH, 2.23+/-0.21 mIU/L; free T4, 1.23+/-0.04 ng/dL) but was not different from those in 10 hyperthyroid patients (LIF, 0.21+/-0.03 ng/mL; TSH, 0.01+/-0.00 mIU/L; free T4, 3.63+/-0.51 ng/dL). Serum LIF concentrations linearly correlated with serum TSH in the 40 samples (r = 0.58, P < 0.001). When T4 (1-8 microg/kg x day) was administered to cynomolgus monkeys with methimazole-induced hypothyroidism, serum T4 and T3 levels increased appropriately, and TSH and LIF concentrations decreased. When methimazole was given alone, both serum TSH (146+/-30 mIU/L) and LIF (8.84+/-0.49 ng/mL) were markedly induced. When methimazole together with T4 (>2 microg/kg x day) was administered, both serum TSH (7.5+/-1.2 mIU/L) and LIF (6.22+/-0.31 ng/mL) were lowered (P < 0.01). Monkey serum LIF levels and log TSH levels also correlated (r = 0.72, P < 0.01). Cultured thyroid carcinoma cells produced LIF (9.2 ng/10(6) cells/48 h). TSH (100 mIU/mL) and interleukin (IL)-6 (10 nmol/L) stimulated in vitro LIF secretion from the cells by 170+/-12% (P < 0.05) and 261+/-8% (P < 0.05), respectively. Dexamethasone (1 micromol/L) inhibited basal LIF concentration by 83% (P < 0.05), whereas TSH and IL-6 stimulated LIF by 52% (P = 0.04) and 42% (P = 0.03), respectively. However, using Northern blot analysis, we could not observe induction of LIF mRNA by TSH, suggesting that LIF regulation by TSH may be due to stimulation of secretion. The results show that the thyroid gland is a source of LIF production; TSH, IL-6, and glucocorticoid influence thyroid cell LIF expression. The correlation between TSH and LIF suggests that LIF may participate in the physiologic regulation of hypothalamic-pituitary-thyroid function.

The neuropeptides, VIP and NPY, that are present in the thyroid nerves are not released into the thyroid vein.

In the present study, we tested the hypothesis that the neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), which are present in the thyroid nerves, act as physiological neurotransmitters involved in the regulation of thyroid hormone secretion and thyroid blood flow. Specifically, we examined whether these neuropeptides can be released into thyroid blood vessels by electrical stimulation of the major thyroid nerves or whether their expression is altered by changes in iodine intake. Sprague-Dawley rats were used in this study. The cervical sympathetic trunk or the superior laryngeal nerve was stimulated by bipolar electrodes in anesthetized rats. During nerve stimulation, blood samples were withdrawn from the thyroid vein. Thyroid blood flow was monitored by laser Doppler blood flowmetry. Sympathetic stimulation caused a marked decrease in thyroid blood flow, which was associated with a significant increase in release of norepinephrine. However, these effects were not accompanied by any change in NPY release into the thyroid vein. Stimulation of the superior laryngeal nerve was not associated with changes in thyroid blood flow or VIP release into the thyroid vein. In a separate experiment, rats were fed a diet containing low-, high-, or normal iodine concentrations. Triiodothyronine (T3) and thyroxine (T4) levels in thyroid venous plasma were significantly reduced in rats fed a low-iodine diet but not in a separate group of rats fed a high iodine diet. However, these treatments had no effect on VIP or NPY concentrations in thyroid venous plasma or in thyroid ganglia. Thus, our results indicate that VIP and NPY, which are present in the thyroid nerves, may not be directly involved in the regulation of thyroid function.

Current concepts of thyroid function and laboratory evaluation

The role of triodothyronine (T(3) in regulating thyroid function is paramount in that at cellular level it interacts with receptors in the nucleus and thereby modulates gene expression. The multiple steps in the processing of lodide by the thyroid gland is under the influence of the thyroid stimulating hormone (TSH). In terms of laboratory evaluation of thyroid function the primary test is TSH. To discriminate between hypothalamic and pitutary dysfunction, the thyroid releasing hormone (TRH) stimulation test is useful. Currently used 2-site Immunometric procedures that employ mouse monoclonal antibodies can be subject to Interference by heterophlle antibodies in patient's serum. Drugs and other extraneous substances can influence the results obtained in some thyroid function tests. Thyroid dysfunction could also be due to autoimmune disease. The limitations of the usefulness of thyroid function tests in non-thyroidal illness should be kept in perspective. In conclusion, the proper interpretation of results of thyroid function tests depends on the sound understanding of concepts of thyroid function and variables affecting laboratory testing.

Long-term effect of norepinephrine on iodide uptake in FRTL-5 cells.

The sympathetic nervous system plays a role in the regulation of thyroid function. In FRTL-5 rat thyroid cells, norepinephrine (NE) acutely depresses intracellular I- by increasing I- efflux. The present study was undertaken to determine the effect of NE on iodide transport after a longer time period. NE inhibited the ability of thyrotropin (TSH) to induce iodide uptake by FRTL-5 cells after 48 or 72 hours, but not after 24 hours. The effect of NE was more evident with increasing concentrations of TSH. NE did not modify the rate of I- efflux. Inhibition was associated with a decrease in the Vmax and no change in the Km for iodide influx. To determine if this was a generalized effect of NE on thyroid cell membrane, the uptake of alpha-aminoisobutyric acid (a nonmetabolizable aminoacid) and of 2-deoxyglucose was measured. NE did not inhibit TSH stimulation of the uptake of the two compounds. NE inhibited the action of dibutyryl cAMP (dbcAMP) on iodide uptake in a similar manner to TSH, but did not alter the cyclic adenosine monophosphate (cAMP) levels increased by TSH. The effects of different adrenoreceptor agonists and antagonists demonstrated that norepinephrine acts through an alpha1-adrenergic receptor.

Normal human intrathyroidal iodine

Excessive or deficient iodine intake results in a variety of human thyroid dysfunction and disorder. The main part in the etiology of these disorders relates to the concentrations of intrathyroidal iodine which is important to regulate thyroid function and state. Instrumental neutron activation and X-ray fluorescent analyses were used to study the age dynamics of intrathyroidal iodine. Concentration and the total content of iodine in the thyroid were estimated in necropsy samples of 70 men and 20 women aged 2–87. Both thyroid lobes were weighed, lyophilised and homogenised. Iodine was analysed in approximately 50-mg samples. The mean intrathyroidal iodine concentration (mean ± S.E.) of a normal subject aged 26–65 averaged 345 ± 21 μg g −1 dry tissue in non-endemic goitre region with no obligatory salt iodination. Maximum iodine concentration was found to be 494 ± 65 μg g −1 ( P < 0.05) for the age of 16–25. A statistically reliable second increase of iodine was shown for the elderly which was 668 ± 60 μg g −1 ( P < 0.001) for the age over 65. Human intact thyroid weight for the age over 15 does not change and averages 14.2 ± 0.4 g. Both left and right lobes of intact thyroid do not differ in weight, iodine concentration and the total content. An inverse correlation was found between thyroid weight and intrathyroidal iodine concentration (−0.32, P < 0.01). The range of intrathyroidal iodine parameters is wide enough to provide a possible explantation for the particular sensitivity of some population to both excessive and deficient iodine intake. Similarity of intrathyroidal iodine age dynamics and incidence of new cases of thyroid carcinoma were to confirm the hypothesis of intrathyroidal iodine importance in cancer etiologies suggested before.

The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology.

I. Introduction II. The Regulation of Thyroid Function in Normal Pregnancy A. The thyroid hormone transport proteins B. The thyroid hormones 1. Total thyroid hormones 2. Free thyroid hormones 3. Peripheral metabolism of thyroid hormones C. The serum levels of thyroglobulin (TG) D. The metabolism of iodine E. The hypothalamic-pituitary control of thyroid function and the role of hCG 1. Hypothalamic-pituitary-thyroid axis (HPTA) 2. Regulation of serum TSH 3. Thyrotropic action of hCG F. A global view of thyroidal economy in pregnancy III. Pathological Alterations of Thyroidal Regulation Associated with Pregnancy A. IDD 1. Consequences of iodine deficiency during pregnancy 2. Assessment of increased thyroidal stimulation 3. Gestational goitrogenesis and its prevention by iodine supplementation 4. Consequences of iodine deficiency for the offspring B. Hypothyroidism and pregnancy 1. Fertility and pregnancy outcome in hypothyroid women 2. Thyroid hormone replacement in the hypothyroid pregnant woman 3. Subclin...

The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology

The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology

Thyroid function and plasma selenium in chronic uremic patients on hemodialysis treatment

It has been shown recently that Selenium (Se), an essential trace element for humans, is involved in the regulation of thyroid function, since the enzyme that catalyzes the liver conversion of the thyroid hormone T4 to the more active form T3 is a selenoenzyme. In chronic uremic patients, low blood Se levels as well as thyroid function abnormalities are often found. The present study was carried out to verify whether any correlation exists between Se levels and thyroid function, and to evaluate possible changes in hormonal pattern during Se supplementation in 10 chronic uremic patients on hemodialysis (HD) treatment. Se was supplemented orally as sodium selenite over six consecutive months. Basic plasma Se levels were significantly lower in patients than in normal controls. Right from the start of Se supplementation, plasma Se concentration promptly normalized and leveled off in the normal range throughout the study. Significant increase of FT3 and reduction of TSH levels were detected during Se supplementation. In Se-supplemented patients, a significant direct correlation was also found between reverse T3 (rT3) and TSH, and a significant inverse correlation was found between Se and TSH. Our results suggest that Se deficiency in chronic uremic patients represents a factor influencing the thyroid function and that the Se status should be determined in the evaluation of thyroid metabolism in these patients.

The Thyroid Hormone Inhibits the Thyrotropin Receptor Promoter Activity: Evidence for a Short Loop Regulation

Thyrotropin, by binding its specific receptor on the plasma membrane of the thyrocyte, regulates thyroid function and differentiation. In FRTL5 cells, thyrotropin down-regulates the thyrotropin receptor (TSHr) promoter activity and induces the transcription of the alpha form of thyroid hormone receptor (TR-α1). In this study we show that the thyrotropin receptor down-regulation, induced by thyrotropin, is mediated by TR-α1. The thyroid hormone receptor binds, in vitro, the thyrotropin receptor minimal promoter and inhibits promoter activity in cotransfections experiments in CV 1 cells. The inhibition is achieved only in the presence of the thyroid hormone. The TSHr promoter mutated in the thyroid hormone receptor binding site does not bind TR, in vitro, and its activity is not inhibited, in cotransfection experiments, in CV 1 cells. The same mutation abolishes the TSH mediated down-regulation of the TSHr promoter activity in FRTL5 thyroid cells. These results support the hypothesis of a regulatory short loop of thyroid hormone in thyroid cells.