Deiodination Of T4 Research Articles

Аллостаз щитовидной железы 2 типа у жителей Якутии

Type 2 thyroid allostasis is a dynamic stress response to changes in thyroid homeostasis that may occur in response to chronic exposure to cold. It is believed that, under these conditions, type 2 allostatic reactions can increase the basal metabolic rate to maintain priority thermogenic mechanisms in the body. For the first time, this work assesses the allostatic response of the thyroid gland among residents of the central region Yakutia with the most extreme climate (from -47°С to -11°С) using a mathematical model called SPINA. The SPINA model reflects the total activity of peripheral deiodinase enzymes (SPINA-GD), as well as the secretory capacity of the thyroid (SPINA-GT). The results showed that the SPINA-GT parameter was within normal limits for all individuals in the study. However, the SPINA-GD parameter was also within normal limits in 30% of those examined, with an increased SPINA-GD value found in 70% of the individuals examined. It was revealed that individuals with elevated SPINA-GD had higher free triiodothyronine (fT3) levels (6.79±0.62 pmol/L) and lower free thyroxine (fT4) levels (13.82±1.51 pmol/L) than those with normal SPINA-GD (fT3=5.96±0.48 pmol/L; fT4=15.37±0.98 pmol/L; p<0.001). This indicates an increased rate of T4 deiodination to T3 in 70% of the most individuals, and the reason for this is likely due to type 2 thyroid allostasis in response to cold stress. Using the SPINA parameters for the first time allows us to identify changes in hypothalamus-pituitary-thyroid axis homeostasis during the winter-spring season among 70% of surveyed residents of Eastern Siberia. Keywords: type 2 thyroid allostasis, SPINA-GT, SPINA-GD, free triiodothyronine (fT3), free thyroxine (fT4), Yakutia.

Noncatalytic Reductive Deiodination of Thyroid Hormones. Electrochemistry and Quantum Chemical Calculations

AbstractNoncatalytic processes may occur spontaneously leading often to undesired products. Electrochemical measurements provide data for thermodynamic calculations. Cyclic voltammetry of thyroxine (T4) and 3,3’,5‐triiodothyronine (T3) in N,N‐dimethylformamide (DMF) and alkaline aqueous solutions of pH 10–14 on glassy carbon electrodes yielded the values of redox potentials for the reduction leading to deiodination of those thyroid hormones under noncatalytic conditions. The first step of T4 deiodination occurs in DMF at −1.93 V vs. Fc+/Fc and for T3 at −1.95 V, which was confirmed by quantum‐chemical calculations at DFT and DLPNO‐CCSD(T) levels. In alkaline aqueous solutions, owing to poor solubility of these compounds, it was possible to determine only approximate values equal to −1.6 to −1.7 V vs. Ag/AgCl for the first step of deiodination. The reduction potentials do not depend on pH under these conditions. As shown by calculations, further steps exhibit very close reduction potentials. The radicals formed as products of concerted dissociative electron transfer to T4 and T3 are relatively kinetically stable which leads to side reactions initiated by radicals in uncatalyzed deiodination processes.

THU230 Consumptive Hypothyroidism Secondary To Hemangioma

Abstract Disclosure: R. Thirunagari: None. D. Taha: None. Background: Peripheral Hypothyroidism also known as consumptive hypothyroidism has been rarely described in association with vascular tumors such as hemangiomas. It is due to excessive production of type 3 iodothyronine deiodinase (D3) enzyme by the hemangioma leading to increased rate of deiodination of T4 and T3 to inactive forms. Clinical case: We report a 4-year-old girl who was diagnosed with consumptive hypothyroidism at the age of 2 months. She was born at full term via scheduled C-section. Mother has hypothyroidism. She was admitted to NICU for respiratory distress and needed oxygen supplementation. She had a large hemangioma covering most of her back on exam. An ultrasound of the head/neck soft tissue showed an ill-defined lobular heterogeneous mass measuring 3.4 x 1.2 x 4.5 cm, markedly hypervascular with both arterial and venous flow likely consistent with hemangioma. At follow up plastic surgery clinic she had respiratory distress which necessitated readmission to the NICU for further workup and possible initiation of Propranolol. An abdominal ultrasound showed enlargement of the right adrenal and on further dedicated ultrasound a right suprarenal lobulated mass as well as intrathoracic soft tissue mass were found. MRI of the abdomen and thorax, revealed multiple large bilateral paraspinal masses throughout the thoracic and lower cervical spine(largest measuring 3.3 x 7 x 15 cm AP) invading the neural foramen at multiple levels, and causing mass effect on the spinal cord which is displaced to the left. There was mass effect on adjacent vascular structures without significant vascular compromise. Biopsy was consistent with hemangioma. Thyroid Newborn screening result was normal. Thyroid evaluation done at 3 months age revealed, free T4 level of 1.04 ng/dL and TSH level of 11.3 µIU/mL. She was started on Levothyroxine 50 mcg daily. Reverse T3 was elevated at 139.2 ng/dl (reference range 13-107 ng/dl) 2 weeks after treatment initiation. She was initiated on propranolol and was followed up by plastic surgery and oncology. She had a very good response to Propranolol. Follow up MRI at 4 years shows almost complete resolution of the mass. She continues to be on Levothyroxine but is requiring smaller dose. Conclusion: Infantile hemangiomas can express high levels of type 3 iodothyronine deiodinase (D3), an enzyme that catalyzes the inner-ring deiodination of T4 to reverse T3 (rT3) and of T3 to 3,3'-diiiodothyronine (T2), both of which are biologically inactive. The hypothyroidism is a result of degeneration of thyroid hormones at rates that exceed the synthetic capacity of the infant's thyroid gland. Our case illustrates the importance of closely monitoring thyroid function tests in infants with large hemangiomas even if newborn thyroid screening result is normal. Some infants may require higher Levothyroxine doses than usual. Hypothyroidism usually resolves after resolution of the mass. Presentation: Thursday, June 15, 2023

Treatment with dexamethasone's effects on pregnant women and their fetuses Guinea pigs' Thyroid and Adrenal Hormones

Among the common small laboratory animals, the guinea pig has a thyroid and adrenal hormone pattern most similar to that in humans. Daily administration of 10mg Dexamethasone s/c from 55 days of pregnancy for 6 days resulted in a depression of fetal body and organ weight and depression of maternal and fetal plasma T4, T3, and cortisol concentration. However, an increase in fetal plasma T4 and T3 concentration rates suggests enhanced de-iodination of T4. In human fetuses, late in gestation, a rise in plasma cortisol may not be necessary for organ maturation. Considerable species differences have been observed concerning the type of hormone secreted by the adrenal cortex. Keywords: Dexamethasone, fetal cortisol, Thyroxin, Triiodothyronine, Guinea pigs.

Chemical Biology of Thyroid Hormones

Thyroid hormones (THs) are synthesized in thyroid follicular cells and secreted by the thyroid gland. These hormones play crucial roles in regulating the body metabolism and temperature, heart rate, neuronal growth, cardiovascular, renal and brain functions. Thyroid gland mainly produces the iodine-containing prohormone L-thyroxine (T4), which undergoes monodeiodination or 5’-deiodination by the selenium- containing iodothyronine deiodinases (DIOs) to generate the biologically active hormone T3. In this general review, the chemical biology aspects of thyroid hormone actions in various organs, biochemical synthesis of T4 in thyroid gland, the role of iodine, thyroglobulin, and thyroid peroxidase in the chemical pathways of hormone synthesis, the transport of hormones by various transport proteins in the blood stream, and various metabolic pathways. The regioselective deiodination of T4 by three isoforms of DIOs to produce active and inactive metabolites and the receptor binding of thyroid hormones are also discussed.

Effect of Occupational Extremely Low-Frequency Electromagnetic Field Exposure on the Thyroid Gland of Workers: A Prospective Study.

The aim of this study was to investigate the biological effects of occupational extremely low-frequency electromagnetic field (ELF-EMF) exposure on the thyroid gland. We conducted a prospective analysis of 85 workers (exposure group) exposed to an ELF-EMF (100 μT, 10-100 Hz) produced by the electromagnetic aircraft launch system and followed up on thyroid function indices, immunological indices, and color Doppler images for 3 years. Additionally, 116 healthy volunteers were randomly selected as controls (control group), the thyroid function of whom was compared to the exposure group. No significant difference was observed in thyroid function between the exposure and control groups. During the follow-up of the exposure group, the serum free triiodothyronine (FT3) level was found to slowly decrease and free thyroxine (FT4) level slowly increase with increasing exposure time. However, no significant difference was found in thyroid-stimulating hormone (TSH) over the three years, and no significant difference was observed in the FT3, FT4 and TSH levels between different exposure subgroups. Furthermore, no significant changes were observed in thyroid autoantibody levels and ultrasound images between subgroups or over time. Long-term exposure to ELF-EMF may promote thyroid secretion of T4 and inhibit deiodination of T4 to T3. ELF-EMF has no significant effect on thyroid immune function and morphology.

Reverse T3 in Patients With Hypothyroidism, Helpful or a Waste of Time?

Abstract Background: Reverse T3 (rT3) is a biologically inactive form of T3 that is created by peripheral 5 deiodination of T4 by type 1 and type 3 deiodinases and may block T3 binding to the thyroid hormone receptor. As about 15% of patients on L-T4 replacement with a normalized TSH report continued fatigue and other hypothyroid symptoms, efforts are needed to understand why this occurs and how it can be corrected. Decades ago, endocrinologists realized that in severe illnesses, rT3 is often high and T3 is often low and termed this “sick euthyroid syndrome”. However, more recently, alternative doctors, including functional medicine doctors, have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor. Without peer-reviewed publications, these functional medicine doctors rely heavily on rT3 levels to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe them L-T3-only preparations to try to lower the rT3. Also poorly characterized in the literature are the effects of hypercortisolism and hypopituitarism, both of which should modulate the expression of deiodinases to increase rT3. Hypotheses: 1) Patient rT3 levels will vary significantly with the type of thyroid medication taken. 2) Patient rT3 levels will be clinically significant in the management of patients on thyroid medications. 3) Hypercortisolism and hypopituitarism will increase rT3 levels. Methods: The most recent rT3 measurements were analyzed from 621 patients currently being managed by TCF. The upper limit of normal for rT3 at either Quest or LabCorp, which is usually 24.1 ng/dL was used as a cut-off for a high result and below 9.2 ng/dL as the low cut-off. Results: Elevate rT3 levels was seen in 3% of patients of patients not on thyroid replacement (5/143), seen in 8% of patients (17/203) taking desiccated thyroid. It was more prevalent in patients taking desiccated thyroid with synthetic T3 (27%, 7/26) or T4 (15%, 16/104) and was seen in 15% of patients (9/58) taking synthetic T4 alone. Changes were made to the amount or type of medications in 199 patients. Levels of rT3 levels were outside the normal range in 27% of these patients (54/199), being above normal range in 16% of these patients (32/199). Hypercortisolism was seen in 37 patients, 36 from Cushing’s disease, however above normal rT3 was seen in only 2 patients. Hypopituitarism was diagnosed in 22 patients, only one had above normal rT3 levels because they couldn’t afford their growth hormone replacement. Conclusion: Measuring rT3 may be helpful in patients who are already on thyroid treatments, and is of greater importance in patients taking synthetic preparations. It is not recommended in patients who are not taking thyroid medicine (even if experiencing hypercortisolism) or in patients with hypopituitarism that are taking adequate hormone replacement.

Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad.

Background: The monocarboxylate transporter 8 (Mct8) protein is a primary thyroxine (T4) and triiodothyronine (T3) (thyroid hormone [TH]) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alter thyroid function and TH metabolism and severely impair neurodevelopment (Allan-Herndon-Dudley syndrome [AHDS]). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is believed that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase, thus preventing brain hypothyroidism. The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knockout (KO) mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, respectively, should be appropriate models of AHDS. Our goal was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KO mice. Methods: We performed RNA sequencing by using RNA from the cerebral cortex and striatum of SH mice and the double KO mice on postnatal days 21-23. Real-time polymerase chain reaction was used to confirm RNA-Seq results in replicate biological samples. Cell type involvement was assessed from cell type-enriched genes. Functional genomic differences were analyzed by functional node activity based on a probabilistic graphical model. Results: Each of the three conditions gave a different pattern of gene expression, with partial overlaps. SH gave a wider and highest variation of gene expression than MD or MO. This was partially due to secondary gene responses to hypothyroidism. The set of primary transcriptional T3 targets showed a tighter overlap, but quantitative gene responses indicated that the gene responses in SH were more severe than in MD or MO. Examination of cell type-enriched genes indicated cellular differences between the three conditions. Conclusions: The results indicate that the neurological impairment of AHDS is too severe to be fully explained by TH deprivation only.

Deiodinases and the Metabolic Code for Thyroid Hormone Action.

Deiodinases modify the biological activity of thyroid hormone (TH) molecules, ie, they may activate thyroxine (T4) to 3,5,3'-triiodothyronine (T3), or they may inactivate T3 to 3,3'-diiodo-L-thyronine (T2) or T4 to reverse triiodothyronine (rT3). Although evidence of deiodination of T4 to T3 has been available since the 1950s, objective evidence of TH metabolism was not established until the 1970s. The modern paradigm considers that the deiodinases not only play a role in the homeostasis of circulating T3, but they also provide dynamic control of TH signaling: cells that express the activating type 2 deiodinase (D2) have enhanced TH signaling due to intracellular build-up of T3; the opposite is seen in cells that express type 3 deiodinase (D3), the inactivating deiodinase. D2 and D3 are expressed in metabolically relevant tissues such as brown adipose tissue, skeletal muscle and liver, and their roles have been investigated using cell, animal, and human models. During development, D2 and D3 expression customize for each tissue/organ the timing and intensity of TH signaling. In adult cells, D2 is induced by cyclic adenosine monophosphate (cAMP), and its expression is invariably associated with enhanced T3 signaling, expression of PGC1 and accelerated energy expenditure. In contrast, D3 expression is induced by hypoxia-inducible factor 1α (HIF-1a), dampening T3 signaling and the metabolic rate. The coordinated expression of these enzymes adjusts TH signaling in a time- and tissue-specific fashion, affecting metabolic pathways in health and disease states.

Halogen Bonding in Biomimetic Deiodination of Thyroid Hormones and their Metabolites and Dehalogenation of Halogenated Nucleosides.

Thyroid hormones (THs) are key players in the endocrine system and play pivotal roles in carbohydrate and fat metabolism, protein synthesis, overall growth, and brain development. The thyroid gland predominantly produces thyroxine or 3,5,3',5'-tetraiodothyronine (T4) as a prohormone; three isoforms of a mammalian selenoenzyme-iodothyronine deiodinase (DIO1, DIO2 and DIO3)-catalyze the regioselective deiodination of T4 to produce biologically active and inactive metabolites. Whereas DIO1 catalyzes both 5- and 5'-deiodination of T4, DIO2 and DIO3 selectively mediate 5- and 5'-deiodination, respectively. In this review we discuss the regioselective deiodination of THs in the presence of organochalcogen compounds. Naphthalene-based compounds containing sulfur and/or selenium at the peri positions mediate regioselective 5-deiodination of THs, detailed mechanistic studies having revealed that the heterolytic cleavage of the C-I bond is facilitated by the formation of cooperative Se/S⋅⋅⋅I halogen bonds and Se/S⋅⋅⋅Se chalcogen bonds. We also discuss the biomimetic deiodination of several TH metabolites, including sulfated THs, iodothyronamines, and iodotyrosines. A brief discussion on the dehalogenation of halogenated nucleosides and nucleobases in the presence of organochalcogen compounds is also included.

Pathophysiological relevance of deiodinase polymorphism

To assess new findings and clinical implications of deiodinase gene polymorphism. Deiodinases are enzymes that can activate or inactivate thyroid hormone molecules. Whereas the types 1 and 2 deiodinase (D1 and D2) activate thyroxine (T4) to 3,5,3'-triiodothyronine (T3) via deiodination of T4's outer ring, D1 and D3 inactivate both T4 and T3 and terminate thyroid hormone action via deiodination of T4's inner molecular ring. A number of polymorphisms have been identified in the three deiodinase genes; the most investigated and likely to have clinical relevance is the Thr92 substitution for Ala substitution in DIO2 (Thr92Ala-DIO2). There are a number of reports describing the association between the Thr92Ala-DIO2 polymorphism and clinical syndromes that include hypertension, type 2 diabetes, mental disorders, lung injury, bone turnover, and autoimmune thyroid disease; but these associations have not been reproduced in all population studies. A new report indicates that carriers of the Thr92Ala-DIO2 polymorphism exhibit lower D2 catalytic activity and localized/systemic hypothyroidism. This could explain why certain groups of levothyroxine-treated hypothyroid patients have improved quality of life when also treated with liothyronine (LT3). Furthermore, Ala92-D2 was abnormally found in the Golgi apparatus, what could constitute a disease mechanism independent of T3 signaling. Indeed, brain samples of Thr92Ala-DIO2 carriers exhibit gene profiles suggestive of brain degenerative disease. In addition, African American carriers of Thr92Ala-DIO2 exhibit an about 30% higher risk of developing Alzheimer's disease. The finding of deiodinase polymorphisms that can diminish thyroid hormone signaling and/or disrupt normal cellular function opens the door to customized treatment of hypothyroidism. Future studies should explore how the racial background modulates the clinical relevance of the Thr92Ala-DIO2 gene polymorphism.

Marked improvement of thyroid function and autoimmunity by Aloe barbadensis miller juice in patients with subclinical hypothyroidism

Some natural compounds decrease serum levels of thyroid autoantibodies, but results are inconsistent and thyroid function has been evaluated infrequently; moreover, the effects of Aloe on thyroid autoimmunity and function have been examined in very few studies. This study stems from the observation of one co-author, who has Hashimoto’s thyroiditis (HT)-related subclinical hypothyroidism (SCH). Upon checking her biochemical thyroid panel when taking daily Aloe barbardensis Miller juice (ABMJ) for thyroid-unrelated reasons, she noticed a decrease in serum thyroperoxidase autoantibodies (TPOAb) and thyrotropin (TSH) and an increase in serum free thyroxine (FT4). Based on this observation, we enrolled 30 consecutive HT women with levothyroxine-untreated SCH and high TPOAb levels. All of them took ABMJ (50 ml daily) for nine months and were tested for serum TSH, FT4, free triiodothyronine (FT3) and TPOAb. Measurements were performed at baseline and at months 3 and 9. TSH, FT4 and TPOAb improved significantly already at month 3 and further (−61%, +23% and −56%) at month 9. However, FT3 decreased significantly at month 3 (−16%) with no further decrease at month 9, so that the FT4:FT3 ratio increased significantly (+33% and + 49%). At baseline, 100% of women had TSH > 4.0 mU/L and TPOAb > 400 U/ml, but frequencies fell to 0% and 37%, respectively, at month 9. In contrast, a control group (namely, 15 untreated SCH women of comparable age and baseline levels of TSH, FT4, FT3 and TPOAb) had no significant changes in any index. We conclude that the daily intake of 100 ml ABMJ for 9 months in women with HT-related SCH decreases the burden of thyroid autoimmune inflammation. In addition, ABMJ rescues thyrocyte function, with decreased need for conversion of the prohormone T4 into the more active T3 through ABMJ-induced inhibition of T4 deiodination.

Adding carbimazole to levothyroxine increases triiodothyronine and improves outcome in patients with primary hypothyroidism: a preliminary study from Egypt.

BackgroundMany hypothyroid patients are not tolerant and not satisfied with levothyroxine (LT4). Older studies used large doses of both carbimazole and LT4 for Hashimoto’s thyroiditis (HT), because Graves’ disease (GD) and HT were considered as very closely related syndromes produced by thyroid autoimmunity.ObjectiveThe aim of the study was to determine the outcome after adding small doses of carbimazole to reduced doses of LT4 for patients with primary hypothyroidism, who are unable to tolerate LT4.MethodsThe study is a non-randomized, single arm, interventional study. It included 19 female patients diagnosed with primary hypothyroidism who could not tolerate LT4. Subjects were recruited from the outpatient clinic of AL-Azhar University Hospital in Damietta, Egypt from January to March 2015. They were divided into two groups; group 1 included 10 patients with HT and 2 patients with non-specified primary hypothyroidism, and group 2 included 7 patients with subtotal thyroidectomy for GD. All patients received carbimazole (10 mg/day) beside LT4 (25 μg thrice/week) for 10 weeks. Statistical analysis of the data was done by SPSS version 20, using paired-sample t-test, ANOVA, Chi square, and Pearson coefficient test.ResultsThere was significant increase in free triiodothyronine (FT3) in addition to significant improvement in depression and LT4 tolerance in the whole population. There was non-significant improvement in TSH in group 1 (p=0.053). Surprisingly, in group 2, in spite of significant increase in TSH (p=0.007) and non-significant decrease in free thyroxine (FT4), there was non-significant increase in FT3. Whether carbimazole improves the pathology of the hypothyroid gland or the peripheral deiodination of T4 to T3 (where the serum and tissue levels of the latter may be responsible for improvement of symptoms) is in need of investigation.ConclusionsAdding carbimazole to LT4 improves FT3, LT4 tolerance, and depression in primary hypothyroid female patients. Further studies are required to determine the appropriate doses of this regimen in different cases.Clinical trial registrationThis study was registered at Thai Clinical Trials Registration center (http://www.clinicaltrials.in.th) with registration ID: TCTR20170123003.FundingThe study received no fund or grant.

A DFT investigation of a bulky biomimetic model catalyzing the 5'-outer ring deiodination of thyroxine.

This paper illustrates the outcomes of a density functional theory investigation aimed at unraveling mechanistic aspects of the 5'-outer ring deiodination process of thyroxine (T4) assisted by the sterically protected organoselenol compound BpqSeH. BpqSeH, which was previously synthesized and tested for its deiodinase activity, is able to afford the active hormone 3,5,3'-tetraiodothyronine (T3) by selective outer-ring deiodination of T4, and to protect the SeH moiety inside the nano-sized molecular cavity from further reactivity, allowing its isolation and characterization. Calculations were also performed including an imidazole ring that, mimicking a His residue in the active site of the original enzyme, plays an crucial role in deprotonating the selenol moiety. Both the suggested enol/keto tautomerization and the previously proven formation of an intermediate whose main characteristic is the presence of a Se⋯I⋯C halogen bond, were examined along the pathway leading to 5'-outer ring deiodination. The calculated potential energy surface showed that neither the pathway encompassing enol/keto tautomerism nor the formation of a halogen bond paving the way to C-I bond breaking and chalcogen-I bond forming is viable. The exergonic formation of the final selenenyl iodide product confirms the stabilization effect of the molecular cavity. Graphical Abstract Computed free energy profile describing the 5'-outer deiodination of thyroxine assisted by the steric hindered organoselenol BpqSH compound. The molecular electrostatic potential map reoported for the INT1 intermediate shows the non-covalent Se-I interaction, due to the attraction between charges of opposite sign, that weakens the C-I bond and prepares the formation of the new Se-I bond.

ChemInform Abstract: Chemistry and Biology in the Biosynthesis and Action of Thyroid Hormones

AbstractReview: [200 refs.

Chemistry and Biology in the Biosynthesis and Action of Thyroid Hormones

Thyroid hormones (THs) are secreted by the thyroid gland. They control lipid, carbohydrate, and protein metabolism, heart rate, neural development, as well as cardiovascular, renal, and brain functions. The thyroid gland mainly produces l-thyroxine (T4) as a prohormone, and 5'-deiodination of T4 by iodothyronine deiodinases generates the nuclear receptor binding hormone T3. In this Review, we discuss the basic aspects of the chemistry and biology as well as recent advances in the biosynthesis of THs in the thyroid gland, plasma transport, and internalization of THs in their target organs, in addition to the deiodination and various other enzyme-mediated metabolic pathways of THs. We also discuss thyroid hormone receptors and their mechanism of action to regulate gene expression, as well as various thyroid-related disorders and the available treatments.

The Effects of Starvation and Refeeding on Oxidative Stress Parameters (MDA, SOD, GPx), Lipid Profile, Thyroid Hormones and Thyroid Histopathology in Male Wistar Rats

Objective: This study aimed to investigate the effect of starvation and re-feeding on oxidative stress markers, lipid profile, thyroid hormones, and changes in thyroid tissue and in male Wistar rats. Method: Fifty-six male Wistar rats were divided into 6 groups. After 3 months of feeding animals with specific diet, the first group was used without fasting (day zero). Other rats were exposed to fasting for 14 days. The second group was considered as a group after fasting (day 14). In groups 3 to 6, replenishment was done and then these groups were euthanized on days 16 to 22, and blood and tissue samples were taken. Results: Significant increase was observed in MDA, triglycerides, and VLDL cholesterol. The concentrations of SOD, GPx and T3 were decreased significantly. By re-feeding, SOD, GPx, triglycerides, total cholesterol, and VLDL cholesterol increased. T3 concentration was significantly increased in all groups after re-feeding. In thyroid tissue, the diameter of follicles and the amount of colloid decreased and the number of parafollicular cells increased during starvation. By days 2 and 4 post-refeeding there were follicles with different sizes and the numbers of parafollicular cells were increased. Conclusion: Starvation may act on the depletion of antioxidants, predisposing subjects to oxidative injury highlights with enhanced level of MDA. Oxidative stress, may play a critical role in the pathophysiology of starvation- refeeding syndrome. Starvation results in a decrease in the serum T3 concentration due to decreased peripheral generation of T3 from T4, because carbohydrates are major regulators of T4 deiodination. The increased free fatty acid availability to the circulation and eventually to the liver contribute to increased VLDL synthesis and elevated plasma triglyceride levels after starvation. The negative effects of oxidative stress in considerable time after re-feeding should be considered in future studies.

Thyroid hormone status affects expression of daily torpor and gene transcription in Djungarian hamsters (Phodopus sungorus)

Thyroid hormones (TH) play a key role in regulation of seasonal as well as acute changes in metabolism. Djungarian hamsters (Phodopus sungorus) adapt to winter by multiple changes in behaviour and physiology including spontaneous daily torpor, a state of hypometabolism and hypothermia. We investigated effects of systemic TH administration and ablation on the torpor behaviour in Djungarian hamsters adapted to short photoperiod. Hyperthyroidism was induced by giving T4 or T3 and hypothyroidism by giving methimazole (MMI) and sodium perchlorate via drinking water. T3 treatment increased water, food intake and body mass, whereas MMI had the opposite effect. Continuous recording of body temperature revealed that low T3 serum concentrations increased torpor incidence, lowered Tb and duration, whereas high T3 serum concentrations inhibited torpor expression. Gene expression of deiodinases (dio) and uncoupling proteins (ucp) were analysed by qPCR in hypothalamus, brown adipose tissue (BAT) and skeletal muscle. Expression of dio2, the enzyme generating T3 by deiodination of T4, and ucps, involved in thermoregulation, indicated a tissue specific response to treatment. Torpor per se decreased dio2 expression irrespective of treatment or tissue, suggesting low intracellular T3 concentrations during torpor. Down regulation of ucp1 and ucp3 during torpor might be a factor for the inhibition of BAT thermogenesis. Hypothalamic gene expression of neuropeptide Y, propopiomelanocortin and somatostatin, involved in feeding behaviour and energy balance, were not affected by treatment. Taken together our data indicate a strong effect of thyroid hormones on torpor, suggesting that lowered intracellular T3 concentrations in peripheral tissues promote torpor.

SERUM T3 LEVEL AND ITS RELATION TO CHRONIC HAPATITIS C VIRUS IN DIABETIC VERSUS NON DIABITIC PATIENTS

Background: Thyroid gland disorders represent one of the commonest endocrine manifestations of chronic hepatitis C (HCV). Objective: This study was performed to evaluate thyroid hormones profile in patients with chronic hepatitis C and its relation to severity of liver damage in the presence or absence of diabetes mellitus. Patients and methods: This study was performed on sixty patients with liver cirrhosis due to hepatitis C virus with or without diabetes mellitus. The patients were divided into three equal groups according to Child-Pough score as following: Group A, group B and group C. All patients were subjected to medical history, clinical examination and laboratory investigations including liver functions tests, renal function tests, complete blood picture (CBC), viral markers for hepatitis, hepatitis C virus antibody (HCV-Ab) and hepatitis B virus antigen (HBs-Ag), polymerase chain reaction (PCR), fasting blood sugar (FBS), postprandial blood sugar(PPBS) hemoglobin A1 C (HbA1c), tetra-iodothyronin (T4), tri-iodothyronin( FT3), thyroid stimulating hormone (TSH) and abdominal ultrasound. Results: Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood platelet and FT3 were significantly lower in group C than group B and group A, while serum levels of bilirubin andprothrombin time(PT) were significantly higher in group C than B and A. Serum levels of FT3 was positively correlated with serum albumin and negatively correlated with serum bilirubin and PT. There were no significant changes in the serum levels of FT3, FT4 and TSH between diabetic and non-diabetic patients. On the other hand, serum levels of ALT, AST, and albumin significantly elevated in diabetic versus non-diabetic patients. Conclusions: A highly significant reduction of serum FT3 in liver cirrhosis with normal serum FT4 and TSH levels was attributive to decreased deiodination of T4 to T3. Decreased serum FT3 level correlated with the severity of liver disease, and may be helpful in assessing the course and diagnosis of liver cirrhosis. Also, serum FT3 hormone level could be used as a marker for grading and assessment of the severity of hepatic dysfunctions.

Editorial: "Thyroid Hormone in Brain and Brain Cells".

Editorial: "Thyroid Hormone in Brain and Brain Cells".