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1.
Proc Natl Acad Sci U S A ; 117(36): 22544-22551, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32826330

RESUMO

Obesity is a major health problem worldwide, given its growing incidence and its association with a variety of comorbidities. Weight gain results from an increase in energy intake without a concomitant increase in energy expenditure. To combat the obesity epidemic, many studies have focused on the pathways underlying satiety and hunger signaling, while other studies have concentrated on the mechanisms involved in energy expenditure, most notably adaptive thermogenesis. Hypothyroidism in humans is typically associated with a decreased basal metabolic rate, lower energy expenditure, and weight gain. However, hypothyroid mouse models have been reported to have a leaner phenotype than euthyroid controls. To elucidate the mechanism underlying this phenomenon, we used a drug-free mouse model of hypothyroidism: mice lacking the sodium/iodide symporter (NIS), the plasma membrane protein that mediates active iodide uptake in the thyroid. In addition to being leaner than euthyroid mice, owing in part to reduced food intake, these hypothyroid mice show signs of compensatory up-regulation of the skeletal-muscle adaptive thermogenic marker sarcolipin, with an associated increase in fatty acid oxidation (FAO). Neither catecholamines nor thyroid-stimulating hormone (TSH) are responsible for sarcolipin expression or FAO stimulation; rather, thyroid hormones are likely to negatively regulate both processes in skeletal muscle. Our findings indicate that hypothyroidism in mice results in a variety of metabolic changes, which collectively lead to a leaner phenotype. A deeper understanding of these changes may make it possible to develop new strategies against obesity.


Assuntos
Hipotireoidismo/metabolismo , Músculo Esquelético/metabolismo , Termogênese/fisiologia , Animais , Modelos Animais de Doenças , Ingestão de Alimentos/fisiologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Musculares/metabolismo , Fenótipo , Proteolipídeos/metabolismo , Simportadores/genética , Simportadores/metabolismo
2.
J Toxicol Sci ; 45(7): 373-390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612006

RESUMO

DEHP (di-2-ethylhexyl phthalate), an environmental endocrine disruptor, is widely used in industrial products, particularly as plasticizers and softeners which could disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis. Rosmarinic acid (RA) possesses potential antioxidant and anti-inflammatory capacities in disease models. Nevertheless, evidence on the association between DEHP-induced thyroid dysfunction and inflammation, as well as the molecular mechanism underlying the protective effects of RA-mitigated DEHP-induced thyroid injury remains inconclusive. Male Sprague Dawley (SD) rats were intragastrically administered DEHP (150 mg/kg, 300 mg/kg, 600 mg/kg) once a day for 90 consecutive days. Also, FRTL-5 cells were treated with a wide range of DEHP concentrations (10-8, 10-7, 10-6, 10-5, 10-4, 10-3, 10-2 M) for 24 hr. Subsequently, RA (50 µM) was administered for 24 hr before 10-4 M DEHP challenge. We found that DEHP induced thyroid damage and inflammatory infiltration in vivo. In addition, we showed that DEHP triggered inflammatory cell death, which is mediated by multiple inflammasomes. Moreover, RA, pyroptosis inhibitor (Ac-YVAD-cmk) and antioxidant inhibitor (NAC) treatment significantly alleviated DEHP-induced thyrocyte death, suppressing pro-inflammatory cytokine production, inhibiting multiple inflammasomes activation and attenuating thyrocyte death, respectively. Collectively, our results reveal that a critical role of inflammasomes activation in DEHP-induced thyroid injury, and suggest that RA confers protection against DEHP-induced thyroid inflammation, and facilitating control of the effects of DEHP after given pyroptosis inhibitor or antioxidant inhibitor. These results indicate that it should be possible to provide novel insights into toxicologically and pharmacologically targeting this molecule to DEHP-induced inflammation.


Assuntos
Anti-Inflamatórios , Antioxidantes , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Depsídeos/farmacologia , Depsídeos/uso terapêutico , Dietilexilftalato/efeitos adversos , Disruptores Endócrinos/efeitos adversos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Inflamassomos/metabolismo , Fitoterapia , Animais , Boraginaceae , Morte Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Dietilexilftalato/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Disruptores Endócrinos/toxicidade , Hipotireoidismo/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Células Epiteliais da Tireoide/efeitos dos fármacos
4.
Med. clín (Ed. impr.) ; 154(1): 1-6, ene. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188676

RESUMO

Introducción: El hígado graso no alcohólico (HGNA) es la enfermedad hepática más prevalente en los países desarrollados y se considera el componente hepático del síndrome metabólico (SM). Últimamente el hipotiroidismo se ha asociado al HGNA, pero nunca se ha estudiado en nuestro entorno. Objetivos: Analizar la relación entre hipotiroidismo (clínico y subclínico) y HGNA. Conocer la asociación de SM con HGNA e hipotiroidismo. Metodología: Estudio transversal, retrospectivo, poblacional en sujetos ≥45 años procedentes de centros de atención primaria de Cataluña e incluidos en la base de datos SIDIAP. Los datos fueron recogidos entre 2009 y 2013. Variables: datos sociodemográficos, comorbilidades, hábitos tóxicos, exploración física, analítica y diagnóstico de SM. Se llevó a cabo un análisis descriptivo y la aplicación de pruebas estadísticas para la comparación de variables. Resultados: Muestra de 10.116 individuos con edad media de 61 (10) años y predominio del sexo femenino (63,6%). La prevalencia de hipotiroidismo fue del 9,1%, sin encontrar diferencias significativas según la presencia de HGNA (p=0,631). El hipotiroidismo se asoció a niveles más elevados de triglicéridos y mayor prevalencia de obesidad (p=0,003). Se detectó mayor alteración de la AST en los individuos con valores incrementados de TSH (p=0,012) y disminuidos de T4L (p=0,037). Las alteraciones en los niveles de hormonas tiroideas no se vincularon con mayor prevalencia de HGNA (TSH p=0,072 y T4L p=0,447). El hipotiroidismo no se asoció como factor de riesgo para el desarrollo de HGNA (OR 0,75; IC 95%: 0,39-1,44; p=0,38). Conclusiones: No se ha demostrado asociación entre el hipotiroidismo y el HGNA. Se necesitan estudios prospectivos para esclarecer la relación entre ambas enfermedades


Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in developed countries and is considered the hepatic component of metabolic syndrome (MetS). Recently hypothyroidism has been associated with NAFLD but has never been studied in Spain. Objectives: To analyze the relationship between hypothyroidism (clinical and subclinical) and NAFLD. To determine the association between MetS with NAFLD and hypothyroidism. Methods: Cross-sectional, retrospective, population study in subjects ≥45 years from primary care centres in Catalonia included in the SIDIAP database. The data was collected between 2009 and 2013. Variables: socio-demographic data, comorbidities, toxic habits, physical examination, analytical tests and diagnosis of MetS. Descriptive analysis and application of statistical tests for the comparison of variables. Results: Sample of 10,116 individuals with a mean age of 61(10) and a predominance of females (63.6%). The prevalence of hypothyroidism was 9.1%, with no significant differences according to the presence of NAFLD (p=.631). Hypothyroidism was associated with higher triglyceride levels and a greater prevalence of obesity (p=.003). Greater alteration of AST was detected in individuals with elevated TSH (p=.012) and decreased levels of T4L (p=.037). Alterations in thyroid hormone levels were not associated with a higher prevalence of NAFLD (TSH p=.072 and T4L p=.447). Hypothyroidism was not considered a risk factor for the development of NAFLD (OR .75; 95% CI: .39-1.44; p=.38). Conclusions: No association was found between hypothyroidism and NAFLD. Prospective studies are needed to clarify a possible relationship between these two diseases


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Hipotireoidismo/epidemiologia , Hipotireoidismo/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Síndrome Metabólica/complicações , Hipotireoidismo/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Espanha/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Obesidade/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia
5.
Arch Physiol Biochem ; 126(1): 7-16, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30145920

RESUMO

Arecoline is known to cause endocrine dysfunction. In the current article role of arecoline on pineal-testis activity was investigated in hypothyroid rats induced by propylthiouracil (PTU). PTU treatment caused thyroid dysfunction ultrastructurally with a fall in T3 and T4 levels followed by a rise of thyroid stimulating hormone (TSH) level. Pineal activity was impaired by PTU treatment, as evident from degenerated synaptic ribbons and mitochondria of the pinealocytes with depletion of pineal and serum N-acetyl serotonin and melatonin levels. Leydig cell function was suppressed, evident from reduced smooth endoplasmic reticulum and depletion of testosterone level. Sex accessories function was impaired by showing scanty rough endoplasmic reticulum with depletion of fructose and sialic acid levels. Arecoline treatment that caused pineal dysfunction and testicular stimulation in control rats, suppressed both pineal and testis functions after PTU treatment. The findings suggest that arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats.


Assuntos
Antitireóideos/efeitos adversos , Arecolina/efeitos adversos , Hipotireoidismo/induzido quimicamente , Glândula Pineal/efeitos dos fármacos , Propiltiouracila/efeitos adversos , Testículo/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Frutose/metabolismo , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Masculino , Melatonina/sangue , Ácido N-Acetilneuramínico/metabolismo , Glândula Pineal/metabolismo , Glândula Pineal/fisiopatologia , Ratos , Serotonina/análogos & derivados , Serotonina/sangue , Testículo/metabolismo , Testículo/fisiopatologia , Testosterona/sangue , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiopatologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
6.
Curr Diabetes Rev ; 16(3): 200-203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31038066

RESUMO

BACKGROUND: Obesity, diabetes mellitus may be related to the health, the relationship and the physiological capacity of the production of thyroid hormones (TH), triiodothyronine (T3) and thyroxine (T4). OBJECTIVES: The main aims of this review are to describe the relationship between obesity, appetite, weight management, hormonal mechanisms of diabetes mellitus and hypothyroidism post-bariatric surgery. METHODOLOGY: An in-depth literature search was conducted to identify scientific studies, which analyzed the correlation between diabetes mellitus and hypothyroidism post-bariatric surgery. RESULTS: Bariatric surgery decreases hypothyroidism, reduces the need for pharmacological action (such as levothyroxine), controls the weight and body fat and increases the sensitivity to leptin and insulin. CONCLUSION: The reduction of the stomach and intestine by bariatric surgery is an evolutionary and beneficial action, because it may lead to a drastic decrease on numbers of conditions such as diabetes, obesity, hypothyroidism, and others. Thus, new studies should also focus on patients' post-operatory conditions, such as lifetime, regulation and functioning of organs after reduced nutrition, and consumption and delivery of nutrients to health maintenance.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus/metabolismo , Hormônios/metabolismo , Hipotireoidismo/metabolismo , Obesidade Mórbida/metabolismo , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/cirurgia , Hormônios/biossíntese , Humanos , Hipotireoidismo/fisiopatologia , Hipotireoidismo/cirurgia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Perda de Peso/fisiologia
7.
J Cardiovasc Pharmacol Ther ; 25(1): 72-85, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31495205

RESUMO

Hypothyroidism is considered a cardiac risk factor, but there is controversial evidence about its effects on coronary disease. The aim of this work was to evaluate the influence of hypothyroidism in rat hearts exposed to 2 degrees of stunning due to ischemia and reperfusion (I/R) as well as the underlying mechanisms. Hypothyroid (HypoT) rats were obtained by drinking 0.02% methimazole during 15 days. Isolated hearts were perfused and introduced in a flow calorimeter to measure contractile performance (P), total heat rate (Ht), and muscle economy (P/Ht). Hearts were exposed to 2 models of I/R, moderate and severe (respectively 20 or 30 minutes I/45 minutes R). Moreover, free cytosolic and mitochondrial calcium changes were measured by confocal fluorometry on cardiomyocytes. Comparison to euthyroid (EuT) hearts was done. Hypothyroidism was cardioprotective, but HypoT hearts were more sensitive than EuT hearts to the preischemic blockade of mitochondrial transporters mNCX and mKATP channels. Moreover, the postischemic recovery of P and P/Ht in HypoT hearts was strongly reduced by inhibition of the cellular pathways of PI3K/Akt and protein kinase C (PKC), and it was increased by nitric oxide synthase (NOS) inhibition. However, physiological concentrations of adrenaline reduced the cardioprotection of HypoT, but oral treatment with 20 mg/kg/day carvedilol prevented it. Results show that hypothyroidism reduces the mitochondrial Ca2+ overload during I/R by mKATP channel activation and Ca2+ extrusion through mNCX, while the PI3K/Akt and PKC pathways are involved in that cardioprotection. Contrarily, NOS activation and adrenaline blunt such cardioprotection, but carvedilol prevented the adrenergic dysfunction. These results would explain why hypothyroidism is a clinical risk factor in angor patients under adrenergic exacerbation but reduced the incidence of acute episodes of coronary syndrome in hospitalized patients. Results suggest that a treatment with carvedilol could be a potential therapeutic agent to prevent cardiac postischemic dysfunction in hypothyroid patients.


Assuntos
Metabolismo Energético , Hipotireoidismo/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Animais , Sinalização do Cálcio , Modelos Animais de Doenças , Feminino , Frequência Cardíaca , Hipotireoidismo/patologia , Hipotireoidismo/fisiopatologia , Preparação de Coração Isolado , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Contração Miocárdica , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Óxido Nítrico Sintase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Canais de Potássio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Trocador de Sódio e Cálcio/metabolismo
8.
Mol Cell Endocrinol ; 499: 110594, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560937

RESUMO

Thyroid hormones have essential roles in regulation of cellular functions, including the immune system. The purinergic signaling, activated through extracellular nucleotides and nucleosides has also strong implications in immune response regulation. Hypothyroidism may involve effects on the immune and purinergic systems. In view of that, we evaluated cytokines levels, their relation with the expression of purinergic enzymes and the effects of this condition on immune system cells from patients with post-thyroidectomy hypothyroidism. Increased IL6, IL10, IL17 and TNF-α levels as well as an increase in CD73 expression in lymphocytes were observed in patients' blood. Moreover, augmented myeloperoxidase activity, lipid peroxidation and thiolgroup production were observed in post-thyroidectomy hypothyroidism. In addition, proliferation and cell death of lymphocytes were enhanced when exposed to patients' serum. This study demonstrates that hypothyroidism is related to changes in the purinergic system, increased cytokines production and oxidative stress, which interfere in the cell life and signaling.


Assuntos
5'-Nucleotidase/sangue , Citocinas/sangue , Hipotireoidismo/cirurgia , Tireoidectomia/efeitos adversos , Regulação para Cima , Adulto , Idoso , Proliferação de Células , Sobrevivência Celular , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Hipotireoidismo/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Soro/química , Transdução de Sinais , Adulto Jovem
9.
Acta Neurobiol Exp (Wars) ; 79(3): 270-275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587019

RESUMO

Cerebrospinal fluid (CSF) contains growth and neurotrophic factors which regulate proliferation, differentiation, and neurogenesis. Thyroid hormones play a crucial role in the development of the nervous system and hypothyroidism during development of embryos leads to defects in the nervous system. This study aimed to survey the effects of rat neonatal CSF collected from induced hypothyroid mothers on differentiation of bone marrow mesenchymal stem cells (BM-MSCs). We hypothesized that hypothyroidism affected levels of growth factor in CSF. To induce hypothyroidism, pregnant Wistar rats received methimazole at the third day of gestation. BM-MSCs were obtained from rat femurs and tibias and cultured in medium. CSF was collected from the cisterna magna of newborn rats, and cells were subsequently exposed to CSF with concentrations of 5,7, and 10 /100 (v/v) for 72 h. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and real time polymerase chain reaction (RT-PCR) were used to quantify the cell viability and analyze the expression of neural markers, respectively. Our morphological studies showed that treatment with hypothyroidism CSF (HTH-CSF) resulted in a significant decrease in neurite growth and proliferation as compared to normal CSF (N-CSF). RT-PCR analysis also showed a significant decrease in expression of neural markers (i.e., Nestin, Neurod-1, NeuN) in cells treated with HTH-CSF as compared with the N-CSF group. The most effective concentration of CSF for BM-MSC differentiation was 5% (V/V). Our results showed a significant decrease in differentiation of BM-MSCs in the presence of neonatal CSF of hypothyroid mothers compared with neonatal CSF of healthy mothers. Thus, thyroid hormones are essential in neural development and hypothyroid defects can affect development of the neonatal brain.


Assuntos
Diferenciação Celular/fisiologia , Hipotireoidismo/líquido cefalorraquidiano , Hipotireoidismo/metabolismo , Células-Tronco Mesenquimais/citologia , Hormônios Tireóideos/deficiência , Animais , Células da Medula Óssea/citologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Hipotireoidismo/induzido quimicamente , Neurônios/citologia , Ratos Wistar
10.
Drugs Aging ; 36(11): 1007-1014, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512083

RESUMO

The age-related resistance to thyroid hormones (THs) explains the paucity of symptoms and signs of hyperthyroidism in older adults and may partly explain the myriad of symptoms and signs of hypothyroidism in biochemically euthyroid older people. This review considers the available data on the mechanisms underlying TH resistance with aging and compares these physiologic changes with the changes observed in congenital TH resistance syndromes. Aging is associated with alterations in TH economy along with a host of changes in the responsiveness of various tissues to THs. The age-related resistance to THs can be attributed to decreased TH transport to tissues, decreased nuclear receptor occupancy, decreased activation of thyroxine to triiodothyronine, and alterations in TH responsive gene expression. Although an increase in serum TH levels is expected in syndromes of TH resistance, unchanged serum TH levels in the euthyroid elderly is the result of increased sensitivity to TH negative feedback with increased suppression of thyroid-stimulating hormone, decreased thyroidal sensitivity to thyroid-stimulating hormone, and decreased TH production and secretion. The current clinical evidence suggests that the age-related TH resistance is mostly an adaptive response of the aging organism. It is tempting to speculate that similar changes can occur prematurely in a group of younger people who present with signs and symptoms of hypothyroidism despite normal serum thyroid function tests.


Assuntos
Envelhecimento/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Hormônios Tireóideos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Animais , Humanos , Hipertireoidismo/genética , Hipotireoidismo/genética , Iodeto Peroxidase/genética , Masculino , Receptores dos Hormônios Tireóideos/genética , Hormônios Tireóideos/sangue , Hormônios Tireóideos/genética , Tiroxina/sangue , Tiroxina/genética , Tiroxina/metabolismo , Tri-Iodotironina/sangue , Tri-Iodotironina/genética , Tri-Iodotironina/metabolismo
11.
Neurochem Res ; 44(9): 2190-2201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31414343

RESUMO

Thyroid disorders impair various functions of the hippocampus where thyroid hormone receptors are localized in the brain. Hyper and hypothyroidism are associated with large changes in brain oxidative stress. Apolipoprotein D (APOD) is a conserved glycoprotein that increased in response to oxidative stress in the brain and has been suggested function as an antioxidant in the brain. Thus, the goal of this work was to explore the effect of maternal hypo- and hyperthyroidism on the Apod expression in the pup's brain regarding changes in oxidative stress. For induction hypo and hyperthyroidism in adult female rats, 100 ppm propylthiouracil (PTU) and 8 ppm levothyroxine administrated 1 month before copulation to the week 3 after delivery in drinking water. The hippocampal region of rat pups was isolated and used for immunohistochemistry and quantitative RT-PCR on postnatal day (PND)5, PND10 and PND20. Results revealed that APOD over-expressed in both hypo- and hyperthyroid groups on PND5, PND10, and PND20. There was a proportional increase between the Apod expression and oxidative stress in the hyperthyroid group but not the hypothyroid in different days. Regarding the wide functions of thyroid hormones, oxidative stress does not suggest to be the only mechanism that involves Apod gene expression in thyroid disturbances.


Assuntos
Apolipoproteínas D/metabolismo , Hipocampo/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Estresse Oxidativo/fisiologia , Animais , Animais Recém-Nascidos , Apolipoproteínas D/genética , Peso Corporal/efeitos dos fármacos , Feminino , Hipocampo/patologia , Hipertireoidismo/patologia , Hipotireoidismo/patologia , Masculino , Neuroproteção/fisiologia , Gravidez , RNA Mensageiro/metabolismo , Ratos Wistar , Tiroxina/farmacologia , Tri-Iodotironina/sangue , Regulação para Cima
12.
Theriogenology ; 138: 145-151, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31352176

RESUMO

Although thyroid hormone (TH) plays important roles in regulating ovarian development, the mechanism are still unclear. Cytochrome P450 lanosterol 14α-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that involved in folliculogenesis and oocyte maturation, which is regulated by follicle stimulating hormone (FSH). However, the effect of TH on CYP51 expression in ovarian cells is unclear. The objective of this study was to determine the effects of TH on CYP51 in rat ovary. Hypothyroidism rats were induced by 6-propyl-2-thiouracil (PTU), genes expressions in ovary were analyzed by Western blot or qRT-PCR. The data showed that CYP51 was significantly decreased in hypothyroidism, which was accompanied by the down-regulation of mRNA level. Meanwhile, similar tendency was also showed in FSHR expression in hypothyroidism. To evaluate the effect of the gonadotropin on CYP51 and FSHR expression in ovarian cells in vivo, hypo rats were injected subcutaneously with equine chorionic gonadotropin (eCG) respectively. The results showed that eCG reversed CYP51 and FSHR expression in hypo group. Moreover, FSH-induced CYP51 expression was meditated by FSHR. In addition, serum concentration of FSH and E2 were also decreased in hypothyroidism, and E2 was up-regulated by eCG treatment. These results indicate that hypothyroidism changes CYP51 and FSHR expression in ovary, which are regulated by gonadotropin. Moreover, genes changes in ovary are at least partially attributed to steroids biosynthesis.


Assuntos
Hipotireoidismo/genética , Ovário/metabolismo , Receptores do FSH/genética , Esterol 14-Desmetilase/genética , Animais , Células Cultivadas , Gonadotropina Coriônica/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios Esteroides Gonadais/biossíntese , Gonadotropinas Equinas/farmacologia , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Ovário/efeitos dos fármacos , Ovário/patologia , Ratos , Ratos Sprague-Dawley , Receptores do FSH/metabolismo , Esterol 14-Desmetilase/metabolismo , Hormônios Tireóideos/farmacologia
13.
Endocr J ; 66(11): 953-960, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31270299

RESUMO

Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT4) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT3 levels and patients with strongly suppressed serum TSH had elevated serum FT3 levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT4 after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT3 levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT4 following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.


Assuntos
Hipotireoidismo/metabolismo , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireotoxicose/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Adolescente , Adulto , Idoso , Apetite , Temperatura Corporal , Temperatura Baixa , Defecação , Feminino , Terapia de Reposição Hormonal , Temperatura Alta , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tireotoxicose/induzido quimicamente , Tireotoxicose/fisiopatologia , Tiroxina/uso terapêutico , Tremor , Adulto Jovem
14.
Int J Neurosci ; 129(10): 1024-1038, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215278

RESUMO

Aim: The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone on the brain tissues oxidative damage and learning and memory impairment in the juvenile hypothyroid rats was evaluated. Main methods: Rats were classified as: ( 1 ) Control; (2) Propylthiouracil (PTU); (3) PTU-Pio 10 and (4) PTU-Pio 20. PTU was given in drinking water (0.05%) during 6 weeks. Pioglitazone (10 or 20 mg/kg) was daily injected intraperitoneally. Passive avoidance (PA) and Morris water maze (MMW) were conducted. Later, the animals were sacrificed and the brain tissues were removed for biochemical measurements. Key funding: The results indicated that in the MWM escape latency as well as traveled path increased in the PTU group as compared to the control group. Also, the time spent in the target quadrant in the probe test of MWM and step-through latency in the PA test were decreased in the PTU group as compared to the control group. Pioglitazone reversed all the negative behavioral effects of hypothyroidism. Administration of PTU attenuated thiol and superoxide dismutase (SOD), and catalase (CAT) activities in the brain tissues, whereas increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. PPARγ agonist improved thiol, SOD and CAT, while diminished MDA concentration. Significance: Our finding in the present study indicated that PPARγ agonist pioglitazone prevented the brain tissues from oxidative damage and learning and memory impairments in juvenile hypothyroid rats.


Assuntos
Lesões Encefálicas/tratamento farmacológico , Hipotireoidismo/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , Pioglitazona/farmacologia , Fatores Etários , Animais , Lesões Encefálicas/metabolismo , Relação Dose-Resposta a Droga , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipotireoidismo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/metabolismo , Estresse Oxidativo/fisiologia , Pioglitazona/uso terapêutico , Ratos , Ratos Wistar , Resultado do Tratamento
15.
Int J Mol Sci ; 20(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212642

RESUMO

Secondary nonalcoholic fatty liver disease (NAFLD) defines those complex pathophysiological and clinical consequences that ensue when the liver becomes an ectopic site of lipid storage owing to reasons other than its mutual association with the metabolic syndrome. Disorders affecting gonadal hormones, thyroid hormones, or growth hormones (GH) may cause secondary forms of NAFLD, which exhibit specific pathophysiologic features and, in theory, the possibility to receive an effective treatment. Here, we critically discuss epidemiological and pathophysiological features, as well as principles of diagnosis and management of some common endocrine diseases, such as polycystic ovary syndrome (PCOS), hypothyroidism, hypogonadism, and GH deficiency. Collectively, these forms of NAFLD secondary to specific endocrine derangements may be envisaged as a naturally occurring disease model of NAFLD in humans. Improved understanding of such endocrine secondary forms of NAFLD promises to disclose novel clinical associations and innovative therapeutic approaches, which may potentially be applied also to selected cases of primary NAFLD.


Assuntos
Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/patologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Animais , Doenças do Sistema Endócrino/metabolismo , Feminino , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/metabolismo , Hipogonadismo/patologia , Hipotireoidismo/epidemiologia , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia
16.
Mol Biol Rep ; 46(4): 3637-3649, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203475

RESUMO

This study aimed to evaluate the anti-hypothyroidism potential of ashwagandha methanolic extract (AME). This target was performed through induction of animal model of hypothyroidism by propylthiouracil. After 1 month from treatments, blood samples were collected for biochemical determinations, and liver and kidney were removed for the determination of oxidative stress markers and thyroid gland was removed for histopathological examination. The total phenolic compounds in the extract and the in vitro radical scavenging activity of extract were also determined. The results revealed that the induction of hypothyroidism by propylthiouracil induced a significant increase in serum TSH level but it induced significant decreases in the levels of total T3, free T3, free T4, and total T4 hormones compared with the control values. Also, serum glucose, Il-6, and body weight gain increased significantly while Il-10 and blood hemoglobin levels showed significant decrease. Induction of hypothyroidism increased also the levels of hepatic and renal MDA and NO and decreased significantly the values of GSH, GPx and Na+/ K+-ATPase. Both AME and the anti-hypothyroidism drug significantly ameliorated the changes occurred in the levels of the above parameters and improved histological picture of thyroid gland but with different degrees; where ashwagandha methanolic extract showed the strongest effect. We can conclude that ashwagandha methanolic extract treatment improves thyroid function by ameliorating thyroid hormones and by preventing oxidative stress.


Assuntos
Hipotireoidismo/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Hormônios Tireóideos/sangue , Animais , Glicemia/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hemoglobinas/metabolismo , Hipotireoidismo/sangue , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Interleucina-10/sangue , Interleucina-6/sangue , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Malondialdeído/metabolismo , Metanol , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Propiltiouracila , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia
17.
J Coll Physicians Surg Pak ; 29(6): S5-S7, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142404

RESUMO

A 55-year female patient presented with subacute thyroiditis (SAT) with a unique dynamic evolution, along with changes in the level of antithyroglobulin antibody, which has been rarely reported. Her thyrotoxicosis gradually worsened over the next three months. Severe hypothyroidism then rapidly developed and did not resolve. For the whole disease course, antithyroglobulin antibody levels were significantly increased, indicating dynamic changes in thyroid function. It has been suggested that the duration of thyrotoxicosis in SAT is highly variable, which is probably related to an underlying autoimmune mechanism. It is therefore, necessary to rule out other causes of thyroiditis.


Assuntos
Autoanticorpos/sangue , Hipotireoidismo/diagnóstico , Tireoidite/diagnóstico , Tireotoxicose/diagnóstico , Feminino , Humanos , Hipotireoidismo/metabolismo , Pessoa de Meia-Idade , Glândula Tireoide/diagnóstico por imagem , Tireoidite/etiologia , Tireoidite/metabolismo , Tireotoxicose/metabolismo , Ultrassonografia
18.
Endokrynol Pol ; 70(2): 190-197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039272

RESUMO

Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: "((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])". No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08-1.24, p < 0.001) to 1.69 (95% CI: 1.21-2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44-0.81, p = 0.001) to 0.92 (95% CI: 0.86-0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Hormônios Tireóideos/metabolismo , Medicina Baseada em Evidências , Humanos , Hipertireoidismo/complicações , Hipotireoidismo/complicações , Fatores de Risco
20.
BMC Res Notes ; 12(1): 294, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31133065

RESUMO

OBJECTIVES: Deficiency as well as excess dietary iodine is associated with several thyroid disorders including Grave's disease and goitre. Previously, cross sectional studies conducted among school children in Nepal showed high prevalence of iodine deficiency. In contrast, recently, few studies have revealed emerging trends of excess urinary iodine concentration in children. This paper, reports excess urinary iodine excretion and thyroid dysfunction among school age children from eastern Nepal. RESULTS: It was a community based cross sectional study in which we measured urinary iodine excretion levels among school age children at baseline and after educational program. The educational program consisted of audio-visual and pamphlets on thyroid health. We also screened them for thyroid function status by physical examination and measuring serum thyroid hormones. Our results show that 34.4% of the children had excess urinary iodine concentration above the WHO recommended levels. Overall, 3.2% of the children were identified to have thyroid dysfunction. Urinary iodine concentration was significantly different between types of salt used and between salt iodine content categories.


Assuntos
Hipertireoidismo/epidemiologia , Hipotireoidismo/epidemiologia , Iodo/urina , Cloreto de Sódio na Dieta/efeitos adversos , Criança , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/metabolismo , Hipertireoidismo/fisiopatologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Hipotireoidismo/fisiopatologia , Iodo/administração & dosagem , Iodo/efeitos adversos , Masculino , Nepal/epidemiologia , Estado Nutricional/fisiologia , Cloreto de Sódio na Dieta/administração & dosagem , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Tireotropina/sangue , Tiroxina/sangue
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