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Thyroid disruptors are found in food, atmosphere, soil, and water. These contaminants interfere with the thyroid function through the impairment of thyroid hormone synthesis, plasma transport, peripheral metabolism, transport into the... more
Thyroid disruptors are found in food, atmosphere, soil, and water. These contaminants interfere with the thyroid function through the impairment of thyroid hormone synthesis, plasma transport, peripheral metabolism, transport into the target cells, and thyroid hormone action. It is well known that iodide uptake mediated by the sodium-iodide symporter (NIS) is the first limiting step involved in thyroid hormones production. Therefore, it has been described that several thyroid disruptors interfere with the thyroid function through the regulation of NIS expression and/or activity. Perchlorate, nitrate, and thiocyanate competitively inhibit the NIS-mediated iodide uptake. These contaminants are mainly found in food, water and in the smoke of cigarettes. Although the impact of the human exposure to these anions is highly controversial, some studies indicated their deleterious effects in the thyroid function, especially in individuals living in iodine deficient areas. Considering the cri...
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ABSTRACT The anterior pituitary gland occupies a central position in the hypothalamus– pituitary glands axes and secretes hormones involved in reproduction, growth, and metabolism. The plasma concentrations of pituitary hormones present... more
ABSTRACT The anterior pituitary gland occupies a central position in the hypothalamus– pituitary glands axes and secretes hormones involved in reproduction, growth, and metabolism. The plasma concentrations of pituitary hormones present fluctuations during the 24 h and are markedly altered during the hypothyroidism. The presence of an intra-pituitary circadian oscillator might be related to these oscillations; however, the molecular mechanism and the consequences of the hypothyroidism are still unknown. The purpose of the present study was to investigate the expression of Bmal1, Per2, Dbp, Nr1d1, Rora, and Dio2 in pituitary during the adult hypothyroidism. For this, euthyroid and thyroidectomized (Tx) male Wistar rats were euthanized during 24 h, every 6 h. The pituitaries were excised and the mRNA expression was evaluated by RT-qPCR. Gapdh and Rpl19 were used as internal control. One and two-way ANOVA, as well as, cosinor analysis were used to evaluate the time-of-day-dependent differential expression for each gene/group and their interactions. The expression of Bmal1, Per2, Dbp, Nr1d1, Rora, and Dio2 presented a circadian pattern in anterior pituitary of euthyroid rats and the peak of Per2, Dpb, Rora, and Dio2 expression occurred at ZT 12, while for Bmal1 was ZT 0/24. In the hypothyroid animals, the circadian pattern of Bmal1, Rora, and Dio2 was lost and the acrophase of Per2, Dbp, and Nr1d1 was advanced about 2.5 h, 3 h, and 45 min respectively. Tx also reduced Mesor values of Dbp and Nr1d1. Our studies reveal that the expression of core clock and clock-controlled genes in anterior pituitary gland are changed during the hypothyroidism and might contribute directly or indirectly to the altered hormonal pattern of secretion observed in this pathological condition. Further studies are in progress to assess this issue. Disclosure This work was supported by the FAPESP (2013/05629-4). DOI: 10.1530/endoabs.37.GP.18.07
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Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid... more
Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid rats, whose cytoskeleton is disarranged. This study investigated the: eEF1A and GH mRNA binding to cytoskeleton plus GH mRNA translation rate and GH secretion, in sham-operated and thyroidectomized rats treated with T3 or saline, and killed 30min thereafter. Thyroidectomy reduced: (a) pituitary F-actin content, and eEF1A plus GH mRNA binding to it; (b) GH mRNA recruitment to polysome; and (c) liver IGF-I mRNA expression, indicating that GH mRNA stability and translation rate, as well as GH secretion were impaired. T3 acutely reversed all these changes, which points toward a nongenomic action of T3 on cytoskeleton rearrangement, which might contribute to the increase on GH mRNA translation rate and GH secretion.
Research Interests: Endocrinology, Biology, Medicine, Cytoskeleton, Biological Sciences, and 15 moreGrowth Hormone, Internal Medicine, Liver, Animals, Male, mRNA stability, Hypothyroidism, Pituitary Gland, Body Weight, Protein Binding, Protein Biosynthesis, Gene Expression Regulation, Polyribosomes, Medical and Health Sciences, and mRNA expression
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Background: Thyroid hormones are known to regulate protein synthesis by acting at transcriptional level inducing the expression of many genes. However, little is known about their role on protein expression at posttranscriptional level,... more
Background: Thyroid hormones are known to regulate protein synthesis by acting at transcriptional level inducing the expression of many genes. However, little is known about their role on protein expression at posttranscriptional level, even though, studies have shown a protein synthesis enhancement associated with mTOR/p70S6K activation after T3 administration. On the other hand, TH actions on translation initiation and polypeptidic chain elongation factors, which are essential to activate protein synthesis, have been poorly explored. Therefore, taking into account that preliminary studies from our laboratory have demonstrated an increase in insulin content in INS-1E cells in response to T3 treatment, the present study aimed to investigate whether proteins from the translational machinery might be involved on the establishment of this effect. Methods: INS-1E cells were maintained in the presence or absence of T3 (10-6M or 10-8M) for 12 h. Thereafter, insulin concentration in the cu...
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A incidência do câncer diferenciado da tiróide vem aumentando há várias décadas no Brasil, assim como em todo o mundo. A popularização de métodos diagnósticos sensíveis e de uso relativamente simples tem contribuído para o diagnóstico... more
A incidência do câncer diferenciado da tiróide vem aumentando há várias décadas no Brasil, assim como em todo o mundo. A popularização de métodos diagnósticos sensíveis e de uso relativamente simples tem contribuído para o diagnóstico cada vez mais freqüente de carcinomas de pequeno tamanho. Uma parte destes tumores ocorre em pacientes denominados de baixo risco, que poderiam se beneficiar de estratégias de conduta menos agressivas. Entretanto, a definição de baixo risco ainda é confusa e não existem meios seguros para distinguir os pacientes que evoluirão de forma pior dos demais. Por outro lado, o uso de novos métodos de acompanhamento vem mudando a maneira de conduzir estes casos. Um grupo multidisciplinar que inclui pesquisadores básicos, endocrinologistas, médicos nucleares, cirurgiões e patologistas endócrinos reviu a literatura pertinente e, com base em sua experiência, propõe algumas normas de conduta no carcinoma diferenciado da tiróide chamado de baixo risco em nosso meio.
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Contractile activity per se induces transcriptional activation of SLC2A4 gene in soleus muscle: involvement of MEF2D, HIF1a and TRα transcriptional factors
Two endocrine bank robbery crews are being searched by the police. As an endocrine system student, you have been summoned to help the police solve the robberies.
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The properties of the sarcoplasmic reticulum membranes isolated from slow-twitch type I soleus and fast-twitch type II psoas muscles of control and thyroxine treated rabbits were comparatively studied. Membrane yield, maximal calcium... more
The properties of the sarcoplasmic reticulum membranes isolated from slow-twitch type I soleus and fast-twitch type II psoas muscles of control and thyroxine treated rabbits were comparatively studied. Membrane yield, maximal calcium storing capacity, ATP-supported calcium uptake, calcium-dependent ATPase activity and calcium-dependent phosphoprotein formation were found to be 3-10 fold higher in psoas than in soleus preparations. Membrane yield, calcium-dependent ATPase activity, ATP-supported calcium transport and calcium-dependent phospho protein are at least twice enhanced in the membranes from soleus muscles of animals treated for 14-21 days with thyroxine. The corresponding capacities of the membranes from psoas muscles are not further augmented by the same thyroxine treatment. The maximal calcium storing capaci ty of the psoas membranes is their sole specific property which is significantly increased. The changes in the properties of the soleus muscles’ sarcoplasmic reticul...
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Thyroid hormones play an important role in glucose metabolism and there is evidence of increased prevalence of thyroid dysfunction in obese and diabetic patients. This study aimed at evaluating the thyroid function and the effects of the... more
Thyroid hormones play an important role in glucose metabolism and there is evidence of increased prevalence of thyroid dysfunction in obese and diabetic patients. This study aimed at evaluating the thyroid function and the effects of the triiodothyronine (T3) treatment on glycemia control, insulin sensitivity and subclinical inflammation in cafeteria-diet-induced obesity in rats. Obesity was induced in male Wistar rats by offering a cafeteria diet and a subset of the obese rats was treated with T3 (1.5 μg per 100 g of body weight) for a 28-day period. The pituitary-thyroid axis was evaluated by molecular and biochemical parameters. Cytokine content was measured in the serum as well as in the mesenteric and epididymal white adipose tissue. Obese rats exhibited impairment of glycemia control, increased content of inflammatory cytokines in mesenteric white adipose tissue, decreased serum thyrotropin (TSH) concentration and increased sodium/iodide symporter (NIS) and TSH receptor (TSHR)...
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Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic... more
Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T3) is an important modulator of heart metabolism and function. Recently, our group has reported time-of-day-dependent rhythms in cardiac T3 sensitivity, as well as, T3-mediated acute alterations on core clock components. Hypo and hyperthyroidism are the second most prevalent endocrine disease worldwide. Considering the importance of the cardiomyocyte circadian clock and T3 to cardiac physiology, the aim of this study was to investigate the consequences of chronic hypo and hyperthyroidism on 24-h rhythms of circadian clock genes in the heart. Hypo and hyperthyroidism was induced in rats by thyroidectomy (Tx) and i.p. injections of supraphysiological dose of T3, respectively. Here we report alterations in mRNA ...
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This study aimed to investigate the consequences of maternal exposure to iodine excess (IE; 0.6 mg NaI/L) throughout pregnancy and lactation on the hypothalamus-pituitary-thyroid axis of the male offspring in adulthood. Maternal IE... more
This study aimed to investigate the consequences of maternal exposure to iodine excess (IE; 0.6 mg NaI/L) throughout pregnancy and lactation on the hypothalamus-pituitary-thyroid axis of the male offspring in adulthood. Maternal IE exposure increased hypothalamic Trh mRNA expression and pituitary Tsh expression and secretion in the adult male offspring. Moreover, the IE-exposed offspring rats presented reduced thyroid hormones levels, morphological alterations in the thyroid follicles, increased thyroid oxidative stress and decreased expression of thyroid differentiation markers (Tshr, Nis, Tg, Tpo, Mct8) and thyroid transcription factors (Nkx2.1, Pax8). Finally, the data presented here strongly suggest that epigenetic mechanisms, as increased DNA methylation, augmented DNA methyltransferases expression, hypermethylation of histone H3, hypoaceylation of histones H3 and H4, increased expression/activity of histone deacetylases and decreased expression/activity of histone acetyltransf...
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Thyroid hormones (THs) classically regulate the gene expression by transcriptional mechanisms. In pituitary, the encoding genes for growth hormone (GH) and thyroid-stimulating hormone (TSH) are examples of genes regulated by... more
Thyroid hormones (THs) classically regulate the gene expression by transcriptional mechanisms. In pituitary, the encoding genes for growth hormone (GH) and thyroid-stimulating hormone (TSH) are examples of genes regulated by triiodothyronine (T3) in a positive and negative way, respectively. Recent studies have shown a rapid adjustment of GH and TSH synthesis/secretion induced by T3posttranscriptional actions. In somatotrophs, T3promotes an increase inGhmRNA content, poly(A) tail length and binding to the ribosome, associated with a rearrangement of actin cytoskeleton. In thyrotrophs, T3reducesTshbmRNA content, poly(A) tail length and its association with the ribosome. In parallel, it promotes a redistribution of TSH secretory granules to more distal regions of the cell periphery, indicating a rapid effect of T3inhibition of TSH secretion. T3was shown to affect the content of tubulin and the polymerization of actin and tubulin cytoskeletons in the whole anterior pituitary gland, and...
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Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal... more
Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal hypothyroidism and deleterious effects in the fetal development. Conversely, the effects of iodine excess (IE) consumption on maternal thyroid function are still controversial. Therefore, this study aimed to investigate the impact of IE exposure during pregnancy and lactation periods on maternal hypothalamus–pituitary–thyroid axis. IE-exposed dams presented reduced serum TH concentration and increased serum thyrotropin (TSH) levels. Moreover, maternal IE exposure increased the hypothalamic expression of Trh and the pituitary expression of Trhr, Dio2, Tsha and Tshb mRNA, while reduced the Gh mRNA content. Additionally, IE-exposed dams presented thyroid morphological alterations, increased thyroid oxidative stress and decreased expression of thyroid genes/protei...
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Iron is an important trace element for proper cell functioning. It is present in cytochromes, hemoglobin and myoglobin (Mb), where it binds to oxygen. It is also an electron acceptor in the respiratory chain. Mb is an 18 kDa heme-protein,... more
Iron is an important trace element for proper cell functioning. It is present in cytochromes, hemoglobin and myoglobin (Mb), where it binds to oxygen. It is also an electron acceptor in the respiratory chain. Mb is an 18 kDa heme-protein, highly expressed in skeletal muscle and heart. The expression of several genes involved in the metabolism of iron is post-transcriptionally regulated by this element. Iron was shown to interfere with the polyadenylation step, modifying their poly (A) tail length and, as a consequence, their stability and translation rate. The aim of this study was to investigate whether iron supplementation or long and short-term restriction affects Mb gene and protein expression, as well as Mb mRNA poly(A) tail length, in cardiac and skeletal muscles of rats. Long-term iron restriction caused an increase in Mb gene and protein expression in Soleus muscle. No changes were observed in extensor digitorum longus muscle and heart. Short-term iron supplementation after ...
Research Interests: Biology, Medicine, Gene expression, Multidisciplinary, Animals, and 4 moreIron, Myoglobin, Skeletal Muscle, and Rats
Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies... more
Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pe...
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TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue... more
TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting th...
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Research Interests: Endocrinology, Biology, Medicine, Gene expression, Muscle strength, and 15 moreErythropoietin, Internal Medicine, Muscular Dystrophy, Animals, Male, Duchenne Muscular Dystrophy, Phenotype, Skeletal Muscle, Dystrophin, Recombinant Proteins, Mdx Mice, Myostatin, Quadriceps, real time polymerase chain reaction, and Medical and Health Sciences
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Research Interests: Biology, Cytokines, Inflammation, Macrophages, Medicine, and 15 moreBiological Sciences, Adipose tissue, Reactive Oxygen Species, Mice, Animals, Male, Mesenchymal Stem Cell, Duchenne Muscular Dystrophy, Phenotype, Biological markers, Dystrophin, Mesenchymal Stromal Cells, Injections, Medical and Health Sciences, and Inflammation Mediators
Research Interests: Endocrinology, Nutrition and Dietetics, Skeletal muscle biology, Biology, Medicine, and 15 moreMuscle strength, Insulin Resistance, Dexamethasone, Spinal Muscular Atrophy, Internal Medicine, Blood Glucose, Insulin, Animals, Male, Dietary Supplements, Nutrients, Rats, Homeostasis, Glucocorticoids, and Leucine
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Research Interests: Endocrinology, Physiology, Chemistry, Biology, Cell Biology, and 15 moreMedicine, Insulin Resistance, Growth Hormone, Internal Medicine, Insulin, Animals, Male, Protein Metabolism, Skeletal Muscle, Rats, Science Technology, Wistar Rats, Biochemistry and cell biology, Myostatin, and Medical biochemistry and metabolomics
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In the present study, the cytotoxicity of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on a macrophage cell line (J774) was investigated. The induction of toxicity was investigated by changes... more
In the present study, the cytotoxicity of palmitic, stearic, oleic, linoleic, arachidonic, docosahexaenoic and eicosapentaenoic acids on a macrophage cell line (J774) was investigated. The induction of toxicity was investigated by changes in cell size, granularity, membrane integrity, DNA fragmentation and phosphatidylserine externalization by using flow cytometry. Fluorescence microscopy was used to determine the type of cell death (Acridine Orange/ethidium bromide assay). The possible mechanisms involved were examined by measuring mitochondrial depolarization, lipid accumulation and PPARγ (peroxisome-proliferator-activated receptor γ) activation. The results demonstrate that fatty acids induce apoptosis and necrosis of J774 cells. At high concentrations, fatty acids cause macrophage death mainly by necrosis. The cytotoxicity of the fatty acids was not strictly related to the number of double bonds in the molecules: palmitic acid>docosahexaenoic acid>stearic acid=eicosapentae...
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Skeletal muscle is a target tissue for approaches that can improve insulin sensitivity in insulin-resistant states. In muscles, glucose uptake is performed by the GLUT-4 protein, which is encoded by the SLC2A4 gene. SLC2A4 gene expression... more
Skeletal muscle is a target tissue for approaches that can improve insulin sensitivity in insulin-resistant states. In muscles, glucose uptake is performed by the GLUT-4 protein, which is encoded by the SLC2A4 gene. SLC2A4 gene expression increases in response to conditions that improve insulin sensitivity, including chronic exercise. However, since chronic exercise improves insulin sensitivity, the increased SLC2A4 gene expression could not be clearly attributed to the muscle contractile activity per se and/or to the improved insulin sensitivity. The present study was designed to investigate the role of contractile activity per se in the regulation of SLC2A4 gene expression as well as in the participation of the transcriptional factors myocyte enhancer factor 2D (MEF2D), hypoxia inducible factor 1a (HIF-1a), and thyroid hormone receptor-α (TRα). The performed in vitro protocol excluded the interference of metabolic, hormonal, and neural effects. The results showed that, in response...
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Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-β increase and... more
Iodide is an important regulator of thyroid activity. Its excess elicits the Wolff-Chaikoff effect, characterized by an acute suppression of thyroid hormone synthesis, which has been ascribed to serum TSH reduction or TGF-β increase and production of iodolipids in the thyroid. These alterations take hours/days to occur, contrasting with the promptness of Wolff-Chaikoff effect. We investigated whether acute iodide administration could trigger events that precede those changes, such as reduction of sodium-iodide symporter (NIS) mRNA abundance and adenylation, and if perchlorate treatment could counteract them. Rats subjected or not to methylmercaptoimidazole treatment (0.03%) received NaI (2,000 μg/0.5 ml saline) or saline intraperitoneally and were killed 30 min up to 24 h later. Another set of animals was treated with iodide and perchlorate, in equimolar doses. NIS mRNA content was evaluated by Northern blotting and real-time PCR, and NIS mRNA poly(A) tail length by rapid amplificat...
Research Interests: Endocrinology, Physiology, Chemistry, Polyadenylation, Medicine, and 15 moreBiological Sciences, Internal Medicine, Animals, Male, American, Medical Physiology, CHEMICAL SCIENCES, mRna expression levels, Rat, Cola, Methimazole, Queue, Biochemistry and cell biology, Gene Expression Regulation, and Medical and Health Sciences
The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to... more
The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to different patterns of gene expression, which might reflect in the permanent expression of several genes in the adulthood. GH gene expression in the pituitary is greatly dependent on TH in the early postnatal life; thus, modifications of thyroid state in NP might lead to alterations in GH gene expression as well as to physiological repercussions in the adult life. This study aimed to investigate this possibility by means of the induction of a neonatal hyperthyroidism in rats (4 μg of 3,5,3′-triiodo-l-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or 30 days, and further evaluation of GH gene expression, as well as its physiological consequences in adult rats subjected to a transient hyperthyroidism in the first 30 days of life. GH mRNA level was ...
Research Interests: Endocrinology, Aging, Biology, Gene expression, Animal Production, and 15 moreGrowth Hormone, Internal Medicine, Female, Animals, Body Composition, Male, Bone Density, Clinical Sciences, Hyperthyroidism, Bone Mineral Density, Hormone, Body Weight, Control Group, Lean Body Mass, and Expression pattern
L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal... more
L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaire...
Research Interests: Exercise Physiology, Life Sciences, Sports Nutrition, Insulin Resistance, Growth Hormone, and 11 moreInsulin, Animals, Male, Dietary Supplements, Arginine, Wistar Rats, Elsevier, Biochemistry and cell biology, Gene Expression Regulation, Pharmacology and pharmaceutical sciences, and physical exertion
TSH, FSH and LH share the same glycoprotein alpha chain (CGA) as part of their protein structure. Therefore, it is possible that thyroid and gonadal dysfunction may affect the CGA expression. This study evaluated several steps of CGA... more
TSH, FSH and LH share the same glycoprotein alpha chain (CGA) as part of their protein structure. Therefore, it is possible that thyroid and gonadal dysfunction may affect the CGA expression. This study evaluated several steps of CGA synthesis and secretion in thyrotrophs and gonadotrophs of control and hypothyroid rats, acutely or chronically-treated with T3. Hypothyroidism increased the Cga mRNA expression and its association to ribosome, but decreased intracellular CGA content. These parameters were reversed after acute or chronic T3 treatment. We conclude that T3 down-regulates Cga mRNA expression, as expected, but also inhibits the association of Cga mRNA to ribosome, as well as the CGA secretion. These findings add novel insights into our understanding of the role of T3 on the regulation of the Cga gene expression and CGA secretion, which might have a potential repercussion in all pituitary glycoproteins hormones synthesis and secretion.
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In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)-treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET,... more
In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)-treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 micrograms/100 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. An addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 +/- 18.55 vs 199.30 +/- 31.47 micrograms/mg, N = 20), and serum (1.95 +/- 0.92 vs 4.26 +/- 1.40 ng/ml, N = 20) TSH concentration (P < 0.001) and also to a decreased in vitro pituitary response to control hypothalamic extracts (55 +/- 8 vs 78 +/- 7%, N = 5, P < 0.005). In addition, hypothalamic extracts of MET-treated rats significantly facilitated in vitro pituitary...
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Whereas it is well known that T3 inhibits TSHβ gene transcription, its effects on TSHβ mRNA stability and translation have been poorly investigated. This study examined these possibilities, by evaluating the TSHβ transcripts poly(A) tail... more
Whereas it is well known that T3 inhibits TSHβ gene transcription, its effects on TSHβ mRNA stability and translation have been poorly investigated. This study examined these possibilities, by evaluating the TSHβ transcripts poly(A) tail length, translational rate and binding to cytoskeleton, in pituitaries of thyroidectomized and sham-operated rats treated with T3 or saline, and killed 30 min thereafter. The hypothyroidism induced an increase of TSHβ transcript poly(A) tail, as well as of its content in ribosomes and attachment to cytoskeleton. The hypothyroid rats acutely treated with T3 exhibited a reduction of TSHβ mRNA poly(A) tail length and recruitment to ribosomes, indicating that this treatment decreased the stability and translation rate of TSHβ mRNA. Nevertheless, acute T3 administration to sham-operated rats provoked an increase of TSHβ transcripts binding to ribosomes. These data add new insight to an important role of T3 in rapidly regulating TSH gene expression at pos...
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Iodide excess acutely downregulates NIS mRNA expression, as already demonstrated. PCCl3 cells treated or not with NaI, NaI+NaClO(4) or NaI+Methimazole, for 30 min to 24 h, were used to further explore how iodide reduces NIS gene... more
Iodide excess acutely downregulates NIS mRNA expression, as already demonstrated. PCCl3 cells treated or not with NaI, NaI+NaClO(4) or NaI+Methimazole, for 30 min to 24 h, were used to further explore how iodide reduces NIS gene expression. NIS mRNA expression was evaluated by Real-Time PCR; its poly(A) tail length, by RACE-PAT; its translation rate, by polysome profile; total NIS content, by Western blotting. NIS mRNA decay rate was evaluated in actinomycin-D-treated cells, incubated with or without NaI for 0-6 h. Iodide treatment caused a reduction in NIS mRNA expression, half-life, poly(A) tail length, recruitment to ribosomes, as well as NIS protein expression. Perchlorate, but not methimazole, prevented these effects. Therefore, reduced poly(A) tail length of NIS mRNA seems to be related to its decreased half-life, in addition to its translation impairment. These data provide new insights about the molecular mechanisms involved in the rapid and posttranscriptional inhibitory effect of iodide on NIS expression.
Research Interests: Chemistry, Medicine, Gene expression, Molecular Mechanics, Biological Sciences, and 15 morereal time PCR, Cell line, Thyroid gland, Animals, Rats, Western blot, Protein Expression, Methimazole, Sodium Compounds, Sodium iodide, Polyribosomes, Pendrin, real time polymerase chain reaction, Tail Length, and Medical and Health Sciences
Glucose transporter 4 (GLUT4) is highly expressed in muscle and fat tissue, where triiodothyronine (T(3)) induces solute carrier family 2 facilitated glucose transporter member 4 (SLC2A4) gene transcription. T(3) was also shown to rapidly... more
Glucose transporter 4 (GLUT4) is highly expressed in muscle and fat tissue, where triiodothyronine (T(3)) induces solute carrier family 2 facilitated glucose transporter member 4 (SLC2A4) gene transcription. T(3) was also shown to rapidly increase glucose uptake in myocytes exposed to cycloheximide, indicating that it might act nongenomically to regulate GLUT4 availability. We tested this hypothesis by evaluating, in thyroidectomized rats (Tx rats), the acute and/or chronic T(3) effects on GLUT4 mRNA expression and polyadenylation, protein content, and trafficking to the plasma membrane (PM) in skeletal muscle, as well as on blood glucose disappearance rate (kITT) after insulin administration. Rats were surgically thyroidectomized and treated with T(3) (0.3 to 100 μg/100 g body weight) from 10 minutes to 5 days, and killed thereafter. Sham-operated (SO) rats were used as controls. Total RNA was extracted from the skeletal muscles (soleus [SOL] and extensorum digitalis longus [EDL]) and subjected to Northern blotting analysis using rat GLUT4 cDNA probe. Total protein was extracted and subjected to specific centrifugations for subcellular fractionation, and PM as well as microsomal (M) fractions were subjected to Western blotting analysis, using anti-GLUT4 antiserum as a probe. GLUT4 mRNA polyadenylation was examined by a rapid amplification of cDNA ends-poly(A) test (RACE-PAT). Thyroidectomy reduced skeletal muscle GLUT4 mRNA, mRNA poly(A) tail length, protein content, and trafficking to the PM, as well as the kITT. The acute T(3) treatment rapidly (30 minutes) increased all these parameters compared with Tx rats. The 5-day T(3) treatment increased GLUT4 mRNA and protein expression, and restored GLUT4 trafficking to the PM and kITT to SO values. The results presented here show for the first time that, in parallel to its transcriptional action on the SLC2A4 gene, T(3) exerts a rapid post-transcriptional effect on GLUT4 mRNA polyadenylation, which might increase transcript stability and translation efficiency, leading to the increased GLUT4 content and availability to skeletal muscle, as well as on GLUT4 translocation to the PM, improving the insulin sensitivity, as shown by the kITT.
Research Interests:
Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW,... more
Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15 days) rats. The fiber type composition of S muscle was also evaluated and used as control of the T3-induced effects. In the S muscle, the T3 treatment increased the Mb mRNA and protein expression, as well as the CS and SDH activity. These changes occurred parallel to the expected increase in type II (fast) and decrease in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was decreased, while the Mb expression and CS activity tended to decrease. In contrast the SDH activity was increased, probably due to the enhanced motor activity that occurs as a short-term response to the hypothermia induced by hypothyroidism. In the EDL, the alterations were milder than those in S muscle in both thyroid states. These findings show that Mb gene expression is induced by T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and provides additional evidence that thyroid hormone increases the aerobic potential of skeletal muscles, as well as the speed of muscle contraction.
Research Interests:
The anterior pituitary contains abundant type II iodothyronine 5&#39;-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that... more
The anterior pituitary contains abundant type II iodothyronine 5&#39;-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T(3)) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T(4)) in a propylthiouracil-insensitive, reverse T(3)-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T(3); in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T(3) levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.