No description available.

Three experiments were conducted to determine the effect of energy, protein, sex, and time on serum T4 and T3 concentrations. All sampling periods occurred at 28-day intervals. In the first experiment, (March-February) 7 adult bucks were placed on 2 feed levels, ad libitum or 25% restricted. Feed consumption of ad libitum deer was highest (P≤0.05) from June-October, fell in November, and remained low through March. Body weights of both groups were highest (P≤0.05) from September-October; lowest from March-April. Serum T4 was highest (P≤0.05) in May and July, and lowest in November. From November-February, restricted deer had lower T4 concentrations (P<0.01) than did ad libitum deer. Serum T3 was highest from May-August; lowest in November. Ad libitum had higher T3 concentrations (P<0.01) than the restricted animals. The second experiment compared the effects of energy and protein on body weight, and serum T4 and T3 of 24 fawns (12 male) from October-May. Feed intake fell gradually to low levels maintained from January-March, then increased slightly. Body weight gain was initially rapid (P<0.01), minimal from November-March, and slow through May. Serum T4 was highest in late April; lowest in October and February. Maximum serum T3 concentrations occurred in April; lowest values in February. Females had higher T4 and T3 values than did males. The third experiment involved 1 adult buck. Blood samples were drawn every 2 hours for a 24-hour period via a jugular catheter. Serum T4 and T3 concentrations were highest from 1600-2000 hours (EST), lowest at 1000 hours. / M.S.

The effect of triiodothyronine (L-T₃) on the protein, RNA and DNA fractions of the thymus nuclei of growth-arrested sulfaguanidine-fed rats has been studied. A single dose of 15 µg of L-T₃ stimulated the incorporation of ¹⁴C-labelled amino acids into total nuclear protein, whole histone and histone fractions. The incorporation of the labelled amino acid into nuclear protein was increased 40 percent over the control 4 hours after the administration of L-T₃. The incorporation of alanine-1-¹⁴C into the total histone fraction reached a maximum 4 hours after the administration of L-T₃ and then decreased 8 and 16 hours after the administration of L-T₃. The incorporation of alanine-1-¹⁴C into histone fraction f₁ reached a maximum at 4 hours after the administration of L-T₃ while the incorporation into fractions f_2a, f_2b and f₃ did not reach a maximum until 8 hours after the administration of L-T₃. Time course studies showed that the protein and RNA moieties of thymus chromatin of rats injected with a single dose of L-T₃ was increased to a maximum at 4 hours. The T_m of chromatin was increased 2° by L-T₃ administration as early as 2 hours. However, the T_m of DNA was not affected. Four hours after the administration of L-T₃ the template efficiency increased 171 percent. The template efficiency of DNA was not affected by L-T₃. These results demonstrate that thyroid hormones modify the chromatin in such a way that the template efficiency is increased. An hypothesis for the mechanism of thyroid hormone action was presented. / Ph. D.

Thyroxine was observed to stimulate the incorporation of radio labeled amino acids into protein of cell-free Liver systems from treated normal and hypothyroid rats. However, the in vitro addition of the hormone only had a stimulatory effect, though quite erratic in magnitude, on the normal system. This difference in response has not been explained. The hypothyroid rat was also characterized by lowered liver ribonucleic acid levels. It WEB found that thyroxine pretreatment resulted in increased ribonucleic acid levels only in the hypothyroid rat with the greater increase occurring in microsomal ribonucleic acid. No change was observed in the ribonucleic acid base ratios of the hypothyroid rat when compared to those of the normal. However, thyroxine pretreatment cf the hypothyroid rat did alter the rate of incorporation of radio phosphorus into the various nucleotides, although there was little difference in the total amount of incorporated label. / Ph. D.

Polychlorinated biphenyls (PCBs) decrease thyroid function in rats and mice by inducing activity of a liver enzyme, uridine diphosphate-glucuronosyltransferase (UDP-GT), thereby increasing thyroxine (T4) clearance. This loss of T4 can lead to hypothyroidism. In this study, an assay was validated for measuring UDP-GT activity toward T4 in Japanese quail (Coturnix japonica). Then UDP-GT induction by Aroclor 1254 was evaluated in quail, and quail and mice were compared in their responses to Aroclor 1254. In Experiment 1, Japanese quail and Balb/c mice were dosed orally with vehicle or Aroclor 1254 (250 or 500 mg/kg) and sacrificed five days later. In Experiment 2, Japanese quail were dosed orally with vehicle or Aroclor 1254 (500 mg/kg) and sacrificed either five or 21 days later. Total liver UDP-GT capacity increased with Aroclor 1254 exposure in all treatment groups of both species. Enzyme induction led to a trend to decreased plasma T4 concentrations at both doses and exposure times in quail and significantly decreased plasma T4 concentrations at both doses in mice. PCBs altered thyroid function in quail, but they did not become hypothyroid. This was in contrast to mice, which did become hypothyroid. It is unclear how PCBs affect the hypothalamic-pituitary-thyroid (HPT) axis in quail, and activation of the HPT axis appears to be inhibited in mice. Overall, quail showed a lesser response than mice to equivalent doses of Aroclor 1254, so it appears that birds may be less vulnerable to PCBs than mammals. / Master of Science

Thyroxine is the main secretory hormone of thyroid gland and it is produced in thyroglobulin by thyroid peroxidase/hydrogen peroxide/iodide system. After biosynthesis and secretion of thyroxine, it undergoes multiple metabolic reactions. The most important metabolic pathway is the stepwise deiodination from the inner ring or outer ring. Removal of one of the outer ring or phenolic ring iodines of biologically less active T4, leads to the formation of 3,5,3'-triiodothyronine or T3, a compound which is biologically more active. On the other hand, removal of one of the inner ring or tyrosyl ring iodines gives 3,3',5'-triiodothyronine (3,3',5'-T3 or rT3) which is a biologically inactive thyroid hormone. Three enzymes involved in this activation and inactivation pathway of thyroid hormones are known as iodothyronine deiodinases (IDs), which are dimeric integral-membrane selenoproteins. Depending upon the sequence and substrate specificity, three iodothyronine deiodinase enzymes have been identified, iodothyronine deiodinase-1 (ID-1), iodothyronine deiodinase-2 (ID-2) and iodothyronine deiodinase-3 (ID-3). ID-1 can catalyze both inner ring and outer ring deiodination of thyroid hormones whereas, ID-2 is selective to the outer ring deiodination. The type-1 and -2 deiodinases (ID-1 and ID-2) produces the biologically active hormone 3,5,3′-triiodothyronine (T3). These two enzymes also convert 3,3′,5′-triiodothyronine (reverse T3 or rT3) to 3,3′-diiodothyronine (3,3′-T2) by outer-ring deiodination (Scheme 1). The type-3 deiodinase (ID-3) catalyzes the convertion of T4 to rT3 by an inner-ring deiodination pathway. Apart from deiodination, there are several alternate pathways of thyroid hormone metabolism, which include sulfate conjugation and glucoronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form thyroacetic acid and thyronamines, respectively. Glucoronidation and sulfate conjugation changes the physico-chemical properties of iodothyronines dramatically. This thesis consists of five chapters. The first chapter provides a general introduction of biosynthesis of thyroid hormones and followed by deiodination by three iodothyronine deiodinase enzyme. This chapter also provides an overview of thyroid hormone transport and different transport proteins and their mode of binding with thyroid hormones. Apart from this, this chapter also provides a brief overview on other thyroid hormone metabolites. In the second chapter of the thesis, initial attempts in the development of different iodothyronine deiodinase mimics have been discussed. Goto et al have shown that the sterically hindered selenol 1 converts the thyroxine derivative 3 (N¬butyrylthyroxine methyl ester) to the corresponding triiodo derivative 4 by an outer-ring deiodination (Scheme 2). Although the reaction was carried out in organic solvent and a relatively higher temperature (50 °C) and longer reaction time (7 days) were required for about 65% deiodination, this study also provides an experimental evidence for the formation of selenenyl iodide (2) in the deiodination of a thyroxine derivative by an organoselenol. However, only one iodine was removed from the outer ring of 3, no inner ring deiodination was detected (Scheme 2). Interestingly, when compound 5 was treated with selenol 1 under similar conditions, no deiodination was observed (Scheme 3). This leads to assumption that presence of free phenolic hydroxyl group is important for the deiodinase activity. Based on this experimental observation, they proposed a mechanism which involves an enol¬keto tautomerism of the phenolic hydroxyl group. In the case of thyroxine, the outer-ring can undergo enol-keto tautomerism, whereas due to lack of free hydroxyl group, the inner ring cannot undergo similar kind of tautomerism. The enol-keto tautomerism probably makes the outer ring iodines more reactive than the inner ring iodines of thyroxine. We have developed tthe first chemmical modell for the inneer ring deioddination of TT4 and T3 by type 33 deiodinase . We have shown that naphthyl-baseed selenol 6 bearing a thhiol group in the cloose proximitty to the sellenium act aas an excelleent model foor ID-3 by selectively deiodinatting T4 andd T3 to prodduce rT3 annd 3,3'-T2, rrespectively,, under physiological relevant conditions. When 2 equuivalent of ccompound 66 was emplooyed in the assay, an almost quuantitative cconversion oof T4 to rT3 was observeed within 300 hours and there was no indicaation of the fformation off T3 or 3,3'-TT2. When the selenol group was repplaced with a thiol group in compouund 7, the ddeiodinase activity wwas decreassed. On thee other handd, when thee thiol groupp was replaaced with selenol mmoiety in commpound 8, thhe deiodinasse activity drramatically iincreased wiithout any change iin the selecttivity. Comppounds 10 and 11 havving N-methhylamino grooup were found too be more aactive than the correspponding unssubstituted ccompounds 7 and 8, respectively. However, introduction of a secondary amine adjacent to the selenol moiety into the compound 9 significantly reduces the deiodinase activity. In the third chapter synthesis, deiodinase activity and mechanism of deiodination of a series of peri-substituted naphthalene derivatives is discussed. Iodobenzene was used as halogen bond donor for the DFT calculations. From the orbital analysis it is observed that there is perfect orbital symmetry match between the HOMO of compound 8 (selenolate form) and LUMO of iodobenzene. When the selenolate form of 1-selenonaphthol interacts with iodobenzene, a halogen bonded adduct is formed. The negative charge on the selenium center decreases as it donates electron pair to the σ* orbital of C–I bond in iodobenzene and as a consequence the positive charge on the iodine center decreases (Figure 1). Addition of iodobenzene to 1-selenonaphthol led to a significant downfield shift in 77Se NMR spectrum of 1-selenonaphthol and with an increase in the concentration of iodobenzene, more downfield shift in the signal was observed. Figure 1. The charges obtained from Natural Bond Orbital (NBO) analysis for the selenolate form of (a) 1-selenonaphthol (b) iodobenzene, (c) halogen-bonded adduct On the basis of experimental end theoretical data, a mechanism for the deiodination of T4 by compound 8 is proposed. According to the mechanism, the initial interaction of one of the selenol moieties with an iodine leads to the formation of halogen bond. The transfer of electron density from selenium to the σ* orbital of the C−I bond generates a σ-hole or partial positive charge on the selenium atom, which facilitates an interaction between the halogen bonded selenium atom and the free selenol (selenolate) moiety (intermediate 12). The selenium−selenium interaction (chalcogen bond) strengthens the halogen bond, leading to a heterolytic cleavage of the C−I bond. The protonation of the resulting carbanion leads to the formation of rT3. On the other hand, the formation of an Se−Se bond produces the diselenide 13 with elimination of iodide as HI. The reductive cleavage of the Se−Se bond in compound 13 regenerates the diselenol 8 (Figure 2). In the fourth chapter deiodination of sulfated thyroid hormones is discussed. Sulfate conjugation is an important step in in the irreversible inactivation of thyroid hormones. Sulfate conjugation of the phenolic hydroxyl group stimulates the inner ring deiodination of T4 and T3 but it blocks the outer ring deiodination of T4 by ID-1. The thyroxine sulfate (T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4. Only ID-1 catalyzes the deiodination of sulfated thyroid hormones. In contrast, ID-2 and ID-3 do not accept T4S and/or T3S as substrate. We have shown that iodothyronine sulfates can be readily deiodinated by synthetic deiodinase model compound 8 and its derivatives. In contrast to the inner ring-selective deiodination of T4, the synthetic compounds loses the selectivity and mediate both inner and outer-ring deiodination of T4S and outer ring deiodination of rT3S. From this study, we have also proposed that the enol-keto tautomerism is probably not required for the outer ring deiodination and the strength of halogen bonding controls the regioselective deiodination by model compounds. In the fifth chapter, the mechanism of inhibition of iodothyronine deiodinases by PTU and IAA is discussed with the help of model compounds. In the model study, it has been observed that compound 8 does not form a stable Se-I intermediate (14), which is essential for the formation of Se-S covalent bond with PTU. As a consequence, the deiodination of T4 by compound 8 is not inhibited by PTU. This study supports the proposal that ID-3 does not follow a ping-pong bi-substrate pathway for deiodination and may not form a stable E-Se-I intermediate, which is responsible for the insensitivity of ID-3 towards PTU. The biphenyl based diselenol 15 reacts with IAA and iodoacetamide to form the corresponding carboxymethylated product 17. On the other hand, compound 8 does not undergo the expected carboxymethylation by IAA and iodoacetamide, but they readily deiodinate both IAA and iodoacetamide. Based on this model study, a possible model is proposed for the insensitivity of ID-3 towards IAA. Iopanoic acid (18) is a well known radiocontrast agent and is used as adjunctive therapy with PTU and CBZ for the treatment of thyrotoxicosis.[9] We show in this chapter that iopanoic acid undergoes monodeiodination by compound 8 under physiological relevant conditions. The deiodinated products (19 and 20) from iopanoic acid are characterized by NMR spectroscopy and single crystal X-ray crystallography. It is observed that after monodeiodination, the strength of halogen bonding decreases and therefore, the monodeiodinated products do not undergo further deiodination.

The anuran Xenopus tropicalis tadpole is an attractive model animal in toxicological evaluation of suspected thyroid disrupting xenobiotics. Due to its reliance of a functioning hypothalamic-pituitary-thyroid (HPT) axis for normal metamorphosis, effects on the HPT axis produces apical endpoints, which are easy to measure. More sensitive endpoints of mRNA expression and histological evaluation of the thyroid gland itself provide strong indications of in vivo thyroid endocrine disruption. X. tropicalis is traditionally exposed in groups of 20 animals in four replicates for each treatment group. However, exposing tadpoles individually can provide stronger statistics and a reduction of total animal sacrifice. In this study we have developed and optimized an individual exposure system by a method development study. This method was then applied in an exposure experiment of a suspected thyroid endocrine disruptor, propylparaben (PrP). Prometamorphotic (NF stage 51) X. tropicalis tadpoles were distributed in three treatment groups (0.05, 0.5 and 5.0 mg PrP/L water) and maintained semi-statically for 14 days. Afterwards, apical measurements (body weight (BW), total body length (BL), snout to vent length (SVL) and hind limb length (HLL)) and reached developmental stage were assessed. In addition, mRNA expression of HPT axis relevant genes encoding deiodinase 2 (D2, hepatic tissue), deiodinase 3 (D3, hepatic and tail tissue) and transthyretin (Ttr, hepatic tissue) were measured by quantitative reverse transcription PCR (qRT-PCR). The PrP exposure did not affect general growth and development, but it did cause a downregulation of dio3 and ttr. The downregulation of dio3 could possibly be associated with a reduced serum content of thyroid hormone, while ttr might be connected to a previously described xenoestrogenic effect of PrP in vitro and in fish.

Résumé : Les anomalies de la contractilité utérine induisent des complications majeures. Il a été décrit que les facteurs inflammatoires et hormonaux déterminent la qualité des contractions utérines. FACTEURS INFLAMMATOIRES : Lors de prématurité spontanée, un statut inflammatoire est présent dans 60 % des cas où des médiateurs lipidiques inflammatoires (leucotriènes, prostaglandines) jouent un rôle majeur. Cette étude évalue l’effet du Montélukast, un antagoniste des récepteurs aux cys-leucotriènes, sur l’activité myométriale humaine in vitro. L’effet du Montélukast anténatal a été quantifié en condition inflammatoire sur l’activité contractile in vitro et sur la prolongation de la grossesse. Deux modèles sont utilisés. Le premier modèle est basé sur le prélèvement de biopsies utérines humaines, lors de césariennes. Le deuxième modèle est basé sur l’induction d’inflammation chez des rates gestantes suivie par des prélèvements utérins. En condition basale, les résultats montrent que le Montélukast a un effet tocolytique significatif sur l’activité contractile in vitro humaine et que son effet est additif à celui de la Nifédipine, le tocolytique de référence. Par ailleurs, l’effet du Montélukast est maximal en condition de prématurité spontanée. Lors de l'ajout d'agent pharmacologique bien caractérisé in vitro dans le modèle inflammatoire, la réactivité contractile à l'ocytocine des biopsies utérines des rates traitées au Montélukast est abolie alors que la sensibilité à la niféfipine était augmentée. Finalement, 3 des 9 rates traitées au Montélukast présentaient une prolongation anormale de la gestation. FACTEURS HORMONAUX : Lors d’une observation fortuite, une modification du patron de contractions utérines a été observée in vitro chez des femmes enceintes présentant une hypothyroïdie et traitées à la T[indice inférieur 4]. Des anomalies de contractilité peuvent conduire à des césariennes avec les risques chirurgicaux associés. Cette partie évalue si cette modification de la contractilité utérine est causée par l’hypothyroïdie sous-jacente ou l’administration de T[indice inférieur 4]. Par des biopsies utérines de rates, nous avons démontré que l’hypothyroïdie réduit la durée et augmente significativement la fréquence des contractions tandis qu’à forte dose de T[indice inférieur 4], une augmentation de la durée et une fréquence diminuée sont quantifiées. Ces résultats miment le patron anormal de contractions observé chez les femmes enceintes traitées à la T[indice inférieur 4]. Nos données suggèrent donc que la modification de la réactivité myométriale est due au traitement à la T[indice inférieur 4]. Cette approche originale montre que ces deux facteurs influencent la contractilité utérine et que des prises en charge plus personnalisées et mieux adaptées permettront de revenir à une contractilité utérine physiologique. / Abstract : Abnormalities of uterine contractility result in major complications. It has been described that inflammatory and hormonal factors determine the quality of uterine contractions. INFLAMMATION FACTORS: In spontaneous prematurity, inflammatory status is present in 60 % of preterm birth cases, where inflammatory lipid mediators (leukotrienes, prostaglandins) play a key role. This section aims to evaluate the effect of montelukast, a cysteinyl-leucotrienes receptor antagonist, on in vitro human myometrial activity. Then, the effect of antenatal montelukast on contractile activity will be quantified under an inflammatory condition in vitro and on the prolongation of the pregnancy. Two models have been used. The first model is based on human uterine biopsies recovered from c-sections. The second model is based on the induction of inflammation in pregnant rats, in which hysterectomies were performed. In the basal condition, montelukast has a tocolytic effect in vitro on human uterine contractile activity and its effect is additive to the effect of nifedipine, the reference tocolytic. Moreover, the effect of montelukast is maximal under spontaneous preterm birth. When adding in vitro pharmacological agent s well characterized to pregnant rats from the inflammatory model, uterine reactivity to oxytocin is abolished after antenatal montelukast treatment while the uterine sensitivity to nifedipine was increased. Finally, three of the nine rats treated with montelukast had an abnormal delay of gestation. HORMONAL FACTORS: After a fortuitous observation, an abnormal pattern of uterine contraction was observed in pregnant women with hypothyroidism and treated with T[subscript 4]. Contractile abnormalities can lead to c-sections with associated surgical risks. This section assesses whether this change in uterine contractility is caused by an underlying hypothyroid condition or the administration of T[subscript 4]. In uterine biopsies from a female rat hypothyroid model, we have demonstrated that hypothyroidism significantly shortens and increases the contractions, while with high doses of T[subscript 4] an increased duration and a decreased frequency were quantified. These results mimic the abnormal pattern of contractions observed in pregnant women treated with T[subscript 4]. Thus, our data suggest that this change in myomterial reactivity is due to T[subscript 4] treatment. This original approach shows that these two factors influence uterine contractility and that appropriate management will allow their uterine contractile activity to return to physiological values.

Este trabalho teve por objetivo avaliar, em seres humanos, se a exposição ao mercúrio acarreta alterações no estado nutricional relativo ao selênio que possam interferir na ativação do hormônio tireoidiano T3. Estas alterações poderiam ocorrer pela redução da disponibilidade do selênio, uma vez que este mineral é considerado um fator protetor contra a intoxicação pelo mercúrio, realizando ligações com o metal e desta forma, inibindo sua absorção; e portanto, a conversão do hormônio tiroidiano T4 em T3 poderia ser prejudicada, tendo em vista que é dependente de selenoproteínas. Alguns estudos têm avaliado a relação entre mercúrio e selênio na população brasileira, no entanto, não têm observado qual o efeito desta interação nos hormônios tiroidianos. A importância deste estudo está em detectar se existem estas alterações, e se elas forem observadas, sugerir formas de melhorar o estado nutricional relativo ao selênio, para minimizar a contaminação por mercúrio e os problemas acarretados pela redução dos níveis circulantes do hormônio tiroidiano ativo. Nesta pesquisa foram formados três grupos, um em Cubatão, um em Novo Airão na região amazônica e, como grupo controle, um em São Paulo. Foi observado que os grupos de Cubatão e São Paulo não se encontram em risco de intoxicação por mercúrio. Já o grupo formado em Novo Airão apresentou teores altos do metal. A ingestão de selênio em todos os grupos apresentou índices de inadequação de consumo acima dos 30%, no entanto, todos se apresentaram adequados em relação aos parâmetros bioquímicos do mineral, e também em relação às concentrações dos hormônios tireoidianos. Nesta pesquisa foi observado que na região amazônica, apesar dos valores elevados de mercúrio, este não provocou efeito no estado nutricional relativo ao selênio e no metabolismo normal dos hormônios tireoidianos. Mais estudos são necessários para que a dinâmica entre selênio e mercúrio seja completamente elucidada, principalmente em regiões onde possa ocorrer exposição aguda ao metal, onde se acredita que as consequências dessa exposição seriam deletérias sobre o status do mineral e suas funções. / The aim of this work was to assess, in human beings, if mercury exposure may lead to changes in selenium status that may interfere with the conversion of active thyroid hormone T3. Changes in selenium status could occur for a reduction in its bioavailability, once the mineral is considered as a protection factor against mercury intoxication, by bounding to the metal and inhibiting its absorption, and so disturbing the conversion of T4 to T3, witch is dependent on selenoproteins. Some researches have assessed the relationship between mercury and selenium in Brazilian population, but these studies did not observed the effects of this interaction in the thyroid hormones concentrations. This research is important because it might detect if there is such interaction, and if it is observed, may suggest viable ways to ameliorate selenium status, reduce mercury contamination risk and the problems that might occur due to reduction on active thyroid hormones concentration. For this research three groups were formed, one in the city of Cubatão, one in Novo Airão in the amazon region, and, as a control group, one in São Paulo city. Is has been observed that the groups of Cubatão and São Paulo are not in risk for mercury intoxication. However, in Novo Airão, the levels of Mercury found were high. Analysis of selenium intake in all groups show that in all of than inadequate rate intake was over 30%, however, in every group biomarkers for selenium were adequate, as well as the thyroid hormone levels. Hence, this study observed that in Amazon region, in spite of high mercury levels, there is no effect in selenium status and in the thyroid hormone. Further investigations are needed to fully elucidate mercury and selenium interaction, especially in regions were an acute exposure to the metal might happen, when the consequences of this mey be deleterious to selenium status and its functions.

O hormônio tireoideano (T3) desempenha papel importante no desenvolvimento, no crescimento e no metabolismo celular. Um dos seus principais efeitos é a ativação do metabolismo basal, contribuindo de forma importante com a regulação do peso corporal, enquanto diminui os níveis plasmáticos de triglicérides e colesterol. A ativação seletiva do receptor <font face=\"Symbol\">&#946 para o hormônio tireoideano (TR) por meio de agonistas seletivos reduziu níveis séricos de colesterol além de aumentar o metabolismo sem causar efeitos indesejáveis sobre o coração, osso ou músculo esquelético. Estes dados sugerem que estes agonistas poderiam ser úteis no tratamento das manifestações da síndrome metabólica tais como obesidade, hipercolesterolemia e resistência à insulina. Dessa forma, estudamos os efeitos da ativação do TR usando um agonista também da série GC, o GC-24, em ratos machos Wistar tratados com dieta rica em gordura e submetidos a injeções diárias de T3 correspondente a 10x a dose fisiológica (30g/g P.C./dia) ou GC-24 em dose equimolar (17g/g P.C./dia). Nosso estudo mostrou que o GC-24 preveniu algumas alterações metabólicas típicas da síndrome metabólica, tais como o aumento da massa gorda, intolerância à glicose e hipertrigliceridemia e corrigiu parcialmente outras como a hipercolesterolemia, o aumento do conteúdo de colesterol hepático e IL-6. Estes achados sugerem um papel importante do TR na mediação dos efeitos do T3 e devem ter repercussão importante na utilização potencial de agonistas seletivos ao TR<font face=\"Symbol\">&#946 como agentes hipocolesterolemiantes / Thyroid hormone (T3) plays an important role in the development, growth and cell metabolism. One of its main effects is to activate the basal metabolic rate significantly contributing to the regulation of body weight, while decreasing serum triglycerides and cholesterol levels. Thyroid hormone receptor selective activation through selective agonists reduced serum cholesterol levels besides increasing metabolic rate without causing undesirable side effects on the heart, bone or skeletal muscle. These data suggest that these agonists could be useful in the treatment of metabolic syndrome manifestations such as obesity, hypercholesterolemia and insulin resistance. Thus, we studied the effects of TR activation also using an agonist from the GC series, the GC-24 in male Wistar rats treated with high fat diet and submitted to daily T3 injections, corresponding to 10x physiological dose (30g/g B.W. /day) or equimolar doses of GC-24 (17g/g P.C. /day). Our study has shown that GC-24 prevented some of the metabolic abnormalities typical of metabolic syndrome such as increase in fat mass, glucose intolerance and hypertriglyceridemia and partially corrected other ones like hypercholesterolemia, the increase in hepatic cholesterol and IL-6 levels. These findings suggest that TR has an important role in the mediating of T3 effects and should have important repercussions in the potential use of selective agonists to TR as cholesterol lowering agents.