Thyroid Hormone Secretion Research Articles

Purinergic signalling in endocrine organs.

There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5'-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.

Hypothyroidism and Cardiovascular Disease: Factors, Mechanism and Future Perspectives

Reduced function of the thyroid gland causes Hypothyroidism which is further attributed to defects in the secretion of thyroid hormones triiodothyronine (T3) and tetra-iodothyronine or thyroxine (T4). T3 and T4 hormones are not only known to regulate the rate of metabolism but also affect the growth and rate of function of many other systems in the body such as neuromuscular, gastrointestinal and cardiovascular system. Hypothyroidism patient usually show higher levels of total cholesterol, low-density lipoproteins (LDL), triglycerides, and other lipid molecules associated with heart disease. The question still remained to be addressed though is whether hypothyroidism affects heart and result in cardiovascular disease. The current review updates us with the recent progress in the hypothyroidism area especially in relation to its connecting link with the heart disease. The present study will further enhance our understanding of the intricacies involved in the secretion of thyroid hormones (T3 & T4) and thyroid stimulating hormone (TSH) subsequently affecting serum lipid levels. The study may help to dice-out cardiovascular risk factors associated with hypothyroidism so that effective measures could be taken prior to occurrence of coronary heart disease.

IGF‐1 receptor deficiency in thyrocytes impairs thyroid hormone secretion and completely inhibits TSH‐stimulated goiter

Although thyroid-stimulating hormone (TSH) is known to be a major regulator of thyroid hormone biosynthesis and thyroid growth, insulin-like growth factor 1 (IGF-1) is required for mediating thyrocyte growth in concert with TSH in vitro. We generated mice with thyrocyte-selective ablation of IGF-1 receptor (TIGF1RKO) to explore the role of IGF-1 receptor signaling on thyroid function and growth. In 5-wk-old TIGF1RKO mice, serum thyroxine (T4) concentrations were decreased by 30% in concert with a 43% down-regulation of the monocarboxylate transporter 8 (MCT8), which is involved in T4 secretion. Despite a 3.5-fold increase in circulating concentrations of TSH, thyroid architecture and size were normal. Furthermore, thyrocyte area was increased by 40% in WT thyroids after 10 d TSH injection, but this effect was absent in TSH-injected TIGF1RKO mice. WT mice treated with methimazole and sodium perchlorate for 2 or 6 wk exhibited pronounced goiter development (2.0 and 5.4-fold, respectively), but in TIGF1RKO mice, goiter development was completely abrogated. These data reveal an essential role for IGF-1 receptor signaling in the regulation of thyroid function and TSH-stimulated goitrogenesis.

How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis

Thyroid stimulating hormone (TSH) activates two major G-protein arms, Gsα and Gq leading to initiation of down-stream signaling cascades for survival, proliferation and production of thyroid hormones. Antibodies to the TSH receptor (TSHR-Abs), found in patients with Graves' disease, may have stimulating, blocking, or neutral actions on the thyroid cell. We have shown previously that such TSHR-Abs are distinct signaling imprints after binding to the TSHR and that such events can have variable functional consequences for the cell. In particular, there is a great contrast between stimulating (S) TSHR-Abs, which induce thyroid hormone synthesis and secretion as well as thyroid cell proliferation, compared to so called “neutral” (N) TSHR-Abs which may induce thyroid cell apoptosis via reactive oxygen species (ROS) generation.In the present study, using a rat thyrocyte (FRTL-5) ex vivo model system, our hypothesis was that while N-TSHR-Abs can induce apoptosis via activation of mitochondrial ROS (mROS), the S-TSHR-Abs are able to stimulate cell survival and avoid apoptosis by actively suppressing mROS. Using fluorescent microscopy, fluorometry, live cell imaging, immunohistochemistry and immunoblot assays, we have observed that S-TSHR-Abs do indeed suppress mROS and cellular stress and this suppression is exerted via activation of the PKA/CREB and AKT/mTOR/S6K signaling cascades. Activation of these signaling cascades, with the suppression of mROS, initiated cell proliferation. In sharp contrast, a failure to activate these signaling cascades with increased activation of mROS induced by N-TSHR-Abs resulted in thyroid cell apoptosis.Our current findings indicated that signaling diversity induced by different TSHR-Abs regulated thyroid cell fate. While S-TSHR-Abs may rescue cells from apoptosis and induce thyrocyte proliferation, N-TSHR-Abs aggravate the local inflammatory infiltrate within the thyroid gland, or in the retro-orbit, by inducing cellular apoptosis; a phenomenon known to activate innate and by-stander immune-reactivity via DNA release from the apoptotic cells.

Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice

Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies to control the regeneration of damaged mucosa.

Current Insights into Animal Models of Graves' Disease and Orbitopathy

Graves' disease (GD) is a systemic autoimmune disease that is characterized by hyperthyroidism, orbitopathy and in rare cases dermopathy. Graves' orbitopathy (GO) is an inflammatory disease of eye and orbit which occurs in about 30-60% of patients. Hyperthyroidism occurs due to the presence of stimulating TSHR-autoantibodies (TRAbs) leading to increased serum levels of thyroid hormones. Attempts to induce Graves' disease in mice by immunization against the hTSHR or its variants have resulted in production of TRAbs that stimulate thyroid follicular cells to increase thyroid hormone secretion. Graves' like orbital changes, such as inflammation, adipogenesis and muscle fibrosis are more difficult to induce. In this review we summarize different methods used to induce murine Graves'-like disease and their impact on murine orbits.

Back to the Basics: Thyroid Gland Structure, Function and Pathology

1. Janelle M. Chiasera, PhD, MT (ASCP)[⇑][1] 1. University of Alabama at Birmingham, Birmingham, Alabama 1. Address for Correspondence: Janelle M. Chiasera, PhD, MT(ASCP) , Chair and Professor, University of Alabama at Birmingham, 1705 University Blvd, SHPB 431, Birmingham, Alabama 35294, 205-975-3111, chiasera{at}uab.edu 1. Explain the HPT feedback system involving the thyroid gland. Include the hormone produced from each gland and the effect of that hormone on the other unit. 2. Describe thyroid hormone synthesis including a description of the 5 steps of hormone production and the rate limiting step to the production of thyroid hormones. 3. Differentiate between hyperthyroidism and hypothyroidism including associated laboratory data, signs and symptoms presented, primary cause, and treatment. 4. Explain the importance of neonatal screening and indicate the type of screening method used by the U.S. 5. Explain the difference between overt and subclinical thyroid disorders and euthyroid sick syndrome and explain what the laboratory data would look like in both conditions. The thyroid gland is one of many glands associated with the endocrine system and it is responsible for the production and secretion of the thyroid hormones, triiodothyronine (T3) and thyroxine (T4). The thyroid gland is located at the front of the neck and is bilobular in structure such that it has a butterfly appearance. The thyroid gland is made up of two cell types, follicular and parafollicular cells. The follicular cells are responsible for producing thyroid hormones. The follicular cells enclose a space called the colloid which contains stored thyroglobulin, a glycoprotein that contains the precursors T3 and T4. The parafollicular cells, also known as C-cells, secrete the hormone calcitonin, a hormone responsible for the regulation of calcium.1-3 The thyroid gland, like other glands of the endocrine system, is controlled through a feedback system involving the hypothalamus, the pituitary, and the target gland (the thyroid). The relationship between the hypothalamus, the pituitary and the thyroid gland is referred to as the HPT axis. The hypothalamus is responsible for producing thyrotropin-releasing hormone (TRH), a tripeptide which is secreted into the venous system that drains to the pituitary gland. At the pituitary, TRH binds to receptors in thyrotroph cells causing the production and secretion of thyroid stimulating hormone (TSH), also known as thyrotropin. Thyroid stimulating hormone binds to TSH receptors in the follicular cells of the thyroid gland causing the production and secretion of thyroid hormones, T3 and T4. As with all endocrine glands, the thyroid gland exhibits both negative and positive… ABBREVIATIONS : AAP - American Academy of Pediatrics; DIT - diiodotryrosine; fT3 - Free T3; fT4 - Free T4; HPT - hypothalamus, pituitary, thyroid axis; MIT - monoiodotryrosine; rT3 - reverse T3; ESS - euthyroid sick syndrome; T3 - triiodothyronine; T4 - thyroxine; TBG - thyroxine-binding globulin; TBPA - thyroxine-binding prealbumin; THBR - thyroid hormone binding ratio; TRH - thyrotropin-releasing hormone; TSH - thyroid stimulating hormone; TT3 - total T3; TT4 - total T4 1. Explain the HPT feedback system involving the thyroid gland. Include the hormone produced from each gland and the effect of that hormone on the other unit. 2. Describe thyroid hormone synthesis including a description of the 5 steps of hormone production and the rate limiting step to the production of thyroid hormones. 3. Differentiate between hyperthyroidism and hypothyroidism including associated laboratory data, signs and symptoms presented, primary cause, and treatment. 4. Explain the importance of neonatal screening and indicate the type of screening method used by the U.S. 5. Explain the difference between overt and subclinical thyroid disorders and euthyroid sick syndrome and explain what the laboratory data would look like in both conditions. [1]: #corresp-1

Effect of deficiency thyroid hormone on superoxide dismutase activity enzyme and their related metals in hypothyroid patients in Basrah Governorate/Iraq.

The maintenance of optimal health requires an adequate supply of carbohydrates, proteins and lipids, and macronutrients, micronutrients, and trace elements. The present study evaluates the lack secretion of thyroid hormones (hyporthyroidism) on antioxidant enzyme which is (superoxide dismutase) and levels of zinc and copper in serum of Iraqi patients with hypothyroid .The results showed a highly significant decrease (p&lt;0.001) in erythrocyte superoxide dismutase(SOD) activity in patients as compared to control .The level of zinc decrease significantly in hypothyroid patients compared with control while the level of copper decreasedin patient group compared with control group but no insignificant (p&gt;0.05) . These results indicated that hypothyroidism increased the free radicals due to decreasing the free radicals scavengers.

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

The aim of metabolic modeling was to understand the cause effect interaction and reliance linked with the complex interactions of biological networks and molecular systems. Drugs that therapeutically modulate the biological processes of disease are often developed with limited knowledge of the underlying complexity of their specific targets. The robustness for systemic modulating behavior of thyroid hormone secretion during the course of different time unit simulation is explained in this study. In this work, a computational model has been developed which mimics the in vivo simulation. The model was constructed with the help of cell designer 4.1 used for analyzing the effect of perturbed amount of drugs at 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 amounts as a unit, targeting Thyroid Peroxidase (TPO), Thyroid Stimulating Hormone Receptor (TSHR), and Sodium Iodide Symporter (NIS). The rate kinetic equations were defined with each reaction to simulate the molecular species dynamic behavior. The modulating behavior of thyroid hormone secretion was analyzed by the process of activation and inactivation states of TPO, TSHR, and NIS at various amounts of drugs. Obtained results explain suitably the entire observable fact of the drug effects and are capable to proceed in response to the perturbations of the natural cell. TSHR was found as the most potent molecular therapeutic target in this study.

Identification, functional analysis, prevalence and treatment of monocarboxylate transporter 8 (MCT8) mutations in a cohort of adult patients with mental retardation

Monocarboxylate transporter 8 (MCT8) is an essential thyroid hormone (TH) transporter as humans with MCT8 mutations have severe neurological and endocrine abnormalities. The objectives are (i) to identify novel MCT8 mutations and (ii) to assess their functional relevance; (iii) to describe the effects of block-and-replace treatment in an MCT8 patient. The TOP-R study is a cross-sectional nation-wide multicentre study. Subjects with unexplained mental retardation (MR) were screened for MCT8 mutations. We identified three mutations: p.F501del (previously described), p.L492P and p.T162T. The F501del and L492P mutants, but not the T162T mutant, showed diminished T3, T4 and rT3 transport in transfected cells. TH transport in T162T fibroblasts was also not affected. One patient was treated with block-and-replace therapy to normalize serum TH levels. The results indicated a slow onset of the decrease in serum T4 and T3 by successive treatment with methimazole and PTU, and eventually their complete normalization by administration of LT4 with PTU but not with methimazole. The frequency of MCT8 mutations in males with X-linked MR approximately 3·9%. We identified several MCT8 mutations in a cohort of subjects with unexplained MR. We demonstrated the pathogenicity of two missense mutations. The synonymous variant did not affect TH transport. Block-and-replace therapy of one patient reversed the TH abnormalities. Our data suggest a decreased TH secretion rate and an increased T4 to T3 conversion by the type I deiodinase in patients with MCT8 mutations. Our study indicates that MCT8 mutations are a relatively frequent cause of X-linked MR.

Modelling TSH and its Receptor Complex for Binding Affinity

Thyroid stimulating hormone (TSH), a glycoprotein hormone consisting of two distinct subunits, binds to its receptor (TSHR) and regulates the production and secretion of thyroid hormones via a complex signaling cascade. Two recent works have reported the crystal structure of stimulating and blocking type antibody-Fab fragments binding to the ectodomain of the TSHR. However, as of today no crystal structure of the TSH-TSHR complex has been reported.In this work, homology modeling of TSH has been carried out with Modeller (Sali and Blundell 1993) using the crystal structure (PDB ID: 1FL7) of the related follicle stimulating hormone (FSH) as the template (Fox, Dias et al. 2001). A fast molecular dynamics minimization of the structure has been performed as part of the Modeller routine. Docking of TSH on the TSHR was carried out on the HEX server (http://hexserver.loria.fr/) and residual contacts of the TSH-TSHR complex have been identified. Conformational studies and the free energy of binding will be reported based on Molecular Dynamics simulations using the AMBER force field. The calculations will be complemented by experimental determination of the binding affinity using Surface Plasmon Resonance (SPR). This study provides useful insight into the kinetics and dynamics of TSH binding to its receptor.Fox, K. M., J. A. Dias, et al. (2001). Molecular Endocrinology 15(3): 378-389.Sali, A. and T. L. Blundell (1993). Journal of Molecular Biology 234(3): 779-815

Синдром нетиреоидных заболеваний при остром бактериальном эндотоксикозе: патогенетические механизмы и методы коррекции

Nonthyroidal illness syndrome is characterized by alterations of thyroid status inpatients with severe nonthyroidal illness who are clinically euthyroid. Mechanisms of nonthyroidal illness syndrome are poorly understood and controversial. Our investigations on nonthyroidal illness syndrome in acute endotoxicosis revealed two principal mechanisms of its development. The peripheral mechanism is the first to develop and referred to disturbance of thyrocytes secretory cycle due to increase of thyroglobulin synthesis, endocytosis and decrease of its proteolytic cleavage. It manifests with drop of serum thyroxine, not triiodthyronine, and increase of serum thyroid stimulating hormone. The central mechanism is associated with hypothalamic-pituitary hypofunction developed simultaneously with systemic inflammatory response. Rate of supplementation of the peripheral mechanism with the central one accounts for different types of nonthyroidal illness syndrome with high, normal and low serum levels of thyroid stimulating hormone. Our research showed that thyroid hormone replacement in nonthyroidal illness syndrome could only suppress thyroid function. Unlike thyroid hormones administration of thyroid stimulating hormone restores thyroid hormone secretion in nonthyroidal illness syndrome, decreases endotoxinemia and secretion of proinflammatory cytokines and improves liver function.

The Relationship between Thyrotropin Receptor Antibody Levels and Intrathyroid Vascularity in Patients with Graves’ Disease

Thyroid stimulating hormone receptor antibodies (TSHRAbs) are specific autoantibodies of Graves' disease (GD). They activate adenylate cyclase, induce thyroid growth, and cause an increased rate of thyroid hormone production and secretion. TSHRAbs levels are decreased by treatment and may predict recurrence when they persist. Theoretically, TSHRAbs levels should be related to intrathyroid vascularity (ITV) due to the autoimmunity and inflammation. We aimed to analyze the relationship between TSHRAbs represented by thyrotropin-binding inhibitory immunoglobulin (TBII) levels and ITV measured by thyroid duplex sonography (TDS). 56 GD patients were prospectively recruited. ITV, measured using TDS, was defined as follows: (average color-flow area in the right and left sides of the thyroid/total thyroid area in transverse view)×100. The average TBII level was 47.1% and average ITV was 27.24. ITV positively and significantly correlated with TBII (p<0.001). TSHRAbs show significant correlation with ITV. This may help doctors to estimate thyroid autoimmune activity when they performing sonography at clinics.

Effects of meat species on the postprandial thermic effect in rats

We examined animal species differences in the postprandial thermic effect of meat and investigated the postprandial thermic effect of mutton in rats. After intake of experimental diets containing each meat, body temperatures of rats fed mutton or venison were significantly higher than that of rats fed rabbit meat. After intake of experimental diets containing fractionized mutton, the body temperatures of rats fed diets containing lean mutton protein were higher than those of rats fed diets without lean mutton protein. In a two-dimensional fluorescence difference gel electrophoresis study of brown adipose tissue, it was shown that the intake of mutton up-regulated the expression of many signaling molecules that are involved in energy metabolism. The postprandial thermic effect of mutton seems to be due not to catecholamine and adrenocorticotropic hormone but to thyroid hormones. The results suggest that intake of lean mutton protein stimulates the secretion of thyroid hormones and facilitates energy metabolism in rats.

English

The hypothalamic-pituitary-thyroid axis is a classical negative feedback loop. It is important for the synthesis and secretion of thyroid hormones namely thyrotropin releasing hormone (TRH), thyroid stimulating hormone (TSH), thyroxine (T4) and tri-iodothyronine (T3) 2 . Low detectable levels of serum T3 stimulate the paraventricular nucleus of the hypothalamus to synthesise and secrete the tri-pepetide TRH. TRH in turn stimulates the thyrotroph cells of the anterior pituitary gland to secrete TSH. This glycoprotein acts on the seven transmembrane G-protein coupled to TSH receptors (TSHR) on the thyroid gland to promote the synthesis and secretion of the prohormone T4 and active hormone T3. Peripheral conversion of T4 to T3 is achieved by type 2 iodothyronine deiodinase enzyme (D2). D2 contributes to 85% of T3 synthesis; 95% of T4 and T3 are primarily bound to thyroxinebinding globulin (TBG). Uptake of free circulating T3 and T4 is determined by three specific cell membrane transporters: monocarboxylate transporters 8, 10 and organic acid transporter protein-1c1. Intracellular levels of iodothyronine deiodinase enzymes type 1 and 2 determine the activity and availability of active T3 2 .

Is There a Relationship Between Fatigue Perception and the Serum Levels of Thyrotropin and Free Thyroxine in Euthyroid Subjects?

Thyrotoxicosis and hypothyroidism are associated with fatigue. Here we studied euthyroid subjects to determine if there was a relationship between serum thyrotropin (TSH), free thyroxine (FT(4)) and thyroperoxidase antibodies and fatigue. A total of 5897 participants of the Nijmegen Biomedical Study received a questionnaire and serum TSH (normal range 0.4-4.0 mIU/L) and FT(4) (normal range 8-22 pmol/L) were measured. Fatigue was evaluated by the RAND-36 and the shortened fatigue questionnaire (SFQ). Euthyroid subjects with a serum TSH level of 0.4-1.0 mIU/L had a lower RAND-36 vitality score (65.2 vs. 66.8; regression coefficient (RC) -1.6 [95% confidence interval (CI) -2.6 to -0.5]; p=0.005) and a higher SFQ score (11.7 vs. 11.0; RC 0.6 [CI 0.2-1.0]; p=0.004) than those with a TSH of 1.0-2.0 mIU/L. Those with a serum FT(4) of 18.5-22 pmol/L reported fatigue more often (52.5% vs. 33.3%; relative risk (RR) 1.4 [CI 1.0-1.9]; p=0.03), had a lower RAND-36 vitality score (61.7 vs. 66.6; RC -4.4 [CI -8.1 to -0.6]; p=0.02) and a higher SFQ score (13.2 vs. 11.0; RC 1.9 [CI 0.4-3.3]; p=0.01) than subjects with a FT(4) level of 11.5-15 pmol/L. In comparison to euthyroid subjects without known thyroid disease, euthyroid subjects with previously known thyroid disease reported fatigue more often (52.3% vs. 34.0%; RR 1.3 [CI 1.0-1.5]; p=0.025), had a lower RAND-36 vitality score (61.4 vs. 66.3; RC -2.9 [CI -5.3 to -0.6]; p=0.015) and a higher SFQ score (13.7 vs. 11.1; RC 1.4 [CI 0.5-2.3]; p=0.002). In euthyroid individuals without a history of thyroid disease, there is a modest relationship between thyroid function and fatigue with subjects having an apparently higher production of T(4) experiencing more fatigue. Subjects with a history of thyroid disease, but with normal TSH and FT(4) concentrations, experience more fatigue than the general population. The reasons for this are unclear, but subtle abnormalities in the dynamics of thyroid hormone secretion should be considered.

Seasonal change of thyroid histomorphological structure and hormone production in yellowfin seabream (Acanthopagrus latus) in the Persian Gulf

Seasonal changes of the thyroid gland structure and hormones secretion was examined in yellowfin seabream (Acanthopagrus latus) in the northwest of Persian Gulf (Musa creek). Thyroid gland composed of follicles scattered around the ventral aorta, near the gills. Follicular cells varied according to secretion of the gland during warm and cold seasons. Thyroid hormones (Triidothyronine [T3] and Thyroxine [T4]) were detected in the fish serum in levels ranged from 4.09-1.30 ng/mL for T3 and from 1.10-0.21 ng/mL for (T4) in the warm and cold seasons, respectively. The results showed that the height of thyroid epithelium and plasma concentration of thyroid hormones (thyroid activity) in A. latus increased significantly during spring and summer. The peak of these factors occurred in midsummer (August). Then, the thyroid activity decreased significantly during autumn and early winter from October to December according to decrease of temperature. T3 and T4 increased significantly from January to April.

Disruption of the Melanin-Concentrating Hormone Receptor 1 (MCH1R) Affects Thyroid Function

Melanin-concentrating hormone (MCH) is a peptide produced in the hypothalamus and the zona incerta that acts on one receptor, MCH receptor 1 (MCH1R), in rodents. The MCH system has been implicated in the regulation of several centrally directed physiological responses, including the hypothalamus-pituitary-thyroid axis. Yet a possible direct effect of the MCH system on thyroid function has not been explored in detail. We now show that MCH1R mRNA is expressed in thyroid follicular cells and that mice lacking MCH1R [MCH1R-knockout (KO)] exhibit reduced circulating iodothyronine (T(4), free T(4), T(3), and rT(3)) levels and high TRH and TSH when compared with wild-type (WT) mice. Because the TSH of MCH1R-KO mice displays a normal bioactivity, we hypothesize that their hypothyroidism may be caused by defective thyroid function. Yet expression levels of the genes important for thyroid hormones synthesis or secretion are not different between the MCH1R-KO and WT mice. However, the average thyroid follicle size of the MCH1R-KO mice is larger than that of WT mice and contained more free and total T(4) and T(3) than the WT glands, suggesting that they are sequestered in the glands. Indeed, when challenged with TSH, the thyroids of MCH1R-KO mice secrete lower amounts of T(4). Similarly, secretion of iodothyronines in the plasma upon (125)I administration is significantly reduced in MCH1R-KO mice. Therefore, the absence of MCH1R affects thyroid function by disrupting thyroid hormone secretion. To our knowledge, this study is the first to link the activity of the MCH system to the thyroid function.

The effect of hyperthyroidism on the levels of liver enzymes in adult male Wistar rats

Thyrotoxicosis is a condition in which tissues are stimulated by increased secretion of thyroid hormone. The most common cause is diffuse toxic goiter and toxic multi-nodular goiter. For more reviews on this disease, the effects of hyperthyroidism on liver enzyme levels were studied. A total of 30 adult male Wistar rats weighing about 190 g were purchased from the Pasteur Institute of Iran. In this study, rats were divided into control group, the group receiving vitamin E, the group receiving levothyroxine, the group receiving levothyroxine treated with vitamin E; blood was taken from all groups over a period of 10 days after injection, and measurement of thyroid hormones and liver tests was made. The findings obtained in this study show that Isolated systolic hypertension (ISH) hormone levels in rats treated with levothyroxine, Treatment with vitamin E may reduce serum levels of ISH , Hormone levels of T4 in the rats treated with levothyroxine were increased compared to normal rates. Treatment with vitamin E reduces serum levels of T4 compared to the first hyper group. T4 hormone levels in rats treated with levothyroxine were reduced compared to normal rates. Treatment with vitamin E may reduce serum levels of T4 compared with the first hyper group. Asparagine Transferase (AST) enzyme levels in rats treated with levothyroxine were increased compared, Treatment with vitamin E may reduce serum levels of AST , Alanine transferase (ALT) enzyme levels in rats treated with levothyroxine were increased , Treatment with vitamin E may increase serum levels of ALT , alkaline phosphatase (ALP) enzyme levels in rats treated with levothyroxine has been increased compared with normal rates. Treatment with vitamin E resulted in serum levels of ALT not to be increased compared with the first group. According to the results of hyperthyroidism and levels of liver enzymes, it can be concluded that hyperthyroidism induced by levothyroxine can increase the levels of hormones T3, T4 and Thyroid Stimulating Hormone (TSH), and then increase the levels of liver enzymes. Treatment of empirical samples with vitamin E is likely to reduce liver damages and prevent the increased levels of liver enzymes compared to empirical samples of hyperthyroidism which have been treated with vitamin E.

Autoimmune Thyrotoxicosis: Diagnostic Challenges

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders.