RESUMO
In humans, the thyroid hormones T3 and T4 are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein thyroglobulin. The overall structure of thyroglobulin is conserved in all vertebrates. Upon thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T4 and T3 at distinct sites. T4 formation involves oxidative coupling between two DIT side chains, and de novo T3 formation involves coupling between an MIT donor and a DIT acceptor. Thyroid hormone synthesis is stimulated by TSH activating its receptor (TSHR), which upregulates the activity of many thyroid gene products involved in hormonogenesis. Additionally, TSH regulates post-translational changes in thyroglobulin that selectively enhance its capacity for T3 formation - this process is important in iodide deficiency and in Graves disease. 167 different mutations, many of which are newly discovered, are now known to exist in TG (encoding human thyroglobulin) that can lead to defective thyroid hormone synthesis, resulting in congenital hypothyroidism.
Assuntos
Tireoglobulina/fisiologia , Glândula Tireoide/metabolismo , Tiroxina/biossíntese , Tri-Iodotironina/biossíntese , Animais , Doença de Graves/diagnóstico , Doença de Graves/genética , Doença de Graves/metabolismo , Humanos , Glândula Tireoide/patologia , Hormônios Tireóideos/biossíntese , Hormônios Tireóideos/genética , Tiroxina/genética , Tri-Iodotironina/genéticaRESUMO
AIMS: To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. MAIN METHODS: Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 µg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. RESULTS: T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. CONCLUSIONS: Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.
Assuntos
Adiponectina/sangue , Hipertireoidismo/metabolismo , Leptina/sangue , Resistina/sangue , Tecido Adiposo/metabolismo , Animais , Peso Corporal , Modelos Animais de Doenças , Regulação da Expressão Gênica , Homeostase , Masculino , Obesidade/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Tireotropina/sangue , Tiroxina/biossíntese , Tri-Iodotironina/biossínteseRESUMO
The effects of aluminium (Al) on thyroid function were evaluated in adult Wistar rats intraperitoneally (i.p) injected with 7 mg Al (as lactate)/kg body weight (b.w) per day during a six week period. The time-course kinetics of Na(125)I (3 µCi per 100 g b.w, i.p) was analysed by measuring gamma-radioactivity of thyroid, serum, serum protein precipitate and bile, at times ranging from 2 to 96 h post-dosing. In Al-treated group the (125)I(-) thyroid uptake at 24 h (15,840 ± 570 vs. 18,030 ± 630 dpm/mg, P<0.05) as well as the rate of (125)I(-) release from the gland, calculated as the slope of the plot between 24 and 96 h (84 ± 8 vs. 129 ± 11 dpm/mg/h, P<0.05) were significantly reduced as compared to control. The biliary (125)I(-) excretion was not modified at all studied times. The Al content and lipid peroxidation (69.1 ± 8.5 vs. 53.2 ± 7.0 nmol MDA/g wet weight, P<0.05) of thyroid tissue were increased in Al-treated rats. The serum concentrations of total thyroxine (T4, 3.78 ± 0.14 vs. 4.68 ± 0.12 µg/dL, P<0.05) and total triiodothyronine (T3, 47 ± 4 vs. 66 ± 5 ng/dL, P<0.05) were decreased by effect of Al, but free-T4 (1.05 ± 0.05 vs. 1.04 ± 0.04 ng/dL, NS) and thyrotropin (TSH, 2.7 ± 0.4 vs. 2.6 ± 0.5 ng/ml, NS) remain unchanged. In spite of the Al could indirectly affect thyroid iodide uptake and hormones secretion by a mechanism involving the induction of an oxidative stress state, however, these changes could be managed by the hypothalamus-pituitary-thyroid endocrine axis. We can conclude that in adult rats the Al would not act as a thyroid disruptor.
Assuntos
Compostos de Alumínio/toxicidade , Lactatos/toxicidade , Compostos Radiofarmacêuticos/metabolismo , Iodeto de Sódio/metabolismo , Glândula Tireoide/efeitos dos fármacos , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Alumínio , Compostos de Alumínio/farmacocinética , Animais , Lactatos/farmacocinética , Peroxidação de Lipídeos , Masculino , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Glândula Tireoide/metabolismo , Tiroxina/biossíntese , Tiroxina/metabolismo , Tri-Iodotironina/biossíntese , Tri-Iodotironina/metabolismoRESUMO
To date, there has been only one in vitro study of the relationship between neuropeptide EI (NEI) and the hypothalamic-pituitary-thyroid (HPT) axis. To investigate the possible relationship between NEI and the HPT axis, we developed a rat model of hypothyroidism and hyperthyroidism that allows us to determine whether NEI content is altered in selected brain areas after treatment, as well as whether such alterations are related to the time of day. Hypothyroidism and hyperthyroidism, induced in male rats, with 6-propyl-1-thiouracil and l-thyroxine, respectively, were confirmed by determination of triiodothyronine, total thyroxine, and thyrotropin levels. All groups were studied at the morning and the afternoon. In rats with hypothyroidism, NEI concentration, evaluated on postinduction days 7 and 24, was unchanged or slightly elevated on day 7 but was decreased on day 24. In rats with hyperthyroidism, NEI content, which was evaluated after 4 days of l-thyroxine administration, was slightly elevated, principally in the preoptic area in the morning and in the median eminence-arcuate nucleus and pineal gland in the afternoon, the morning and afternoon NEI contents being similar in the controls. These results provide the bases to pursue the study of the interaction between NEI and the HPT axis.
Assuntos
Encéfalo/metabolismo , Hipertireoidismo/metabolismo , Hipotireoidismo/metabolismo , Eminência Mediana/metabolismo , Oligopeptídeos/biossíntese , Hipófise/metabolismo , Glândula Tireoide/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/fisiopatologia , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/fisiopatologia , Masculino , Eminência Mediana/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Propiltiouracila/efeitos adversos , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Glândula Tireoide/efeitos dos fármacos , Tireotropina/biossíntese , Tiroxina/efeitos adversos , Tri-Iodotironina/biossínteseRESUMO
This work aimed at verifying the influence of propyl-thiouracil (PTU)-induced thyroid hormone deficiency on gingival mucosa of young male rats, measuring total protein concentration, collagen content and DNA concentration as indices of cellular population. Fifty Sprague-Dawley rats were used. The animals were grouped in: PTU-treated (i.p. 10 mg/d) and control rats (C). The experience was maintained for a period of 10 weeks. Total protein content of gingival mucosa tissue was determined by the Lowry method; hydroxyprolin rate, as prototype amino acid of collagen, was determined using the Newman method, and DNA concentration was measured by Burton's methodology. The results showed decreased amounts of PTU-treated rats gingival total protein content (PTU= 41.23 +/- 24.05 vs. C= 63.36 +/- 18.05); no alterations were seen in hydroxyprolin concentration neither in DNA content of PTU treated rats, respectively (PTU= 2.18 +/- 1.48 vs. C= 2.29 +/- 1.51) and (PTU= 0.33 +/- 0.19 vs. C= 0.46 +/- 0.41). Thus, PTU treatment promotes a decrease in total protein content of rat gingival mucosa that may be interpreted as a decrease in protein synthesis induced by the hypothyroid condition, but with no alteration either in collagen or nucleic acid rates.
Assuntos
Antitireóideos , Colágeno/análise , Gengiva/química , Hipotireoidismo/induzido quimicamente , Propiltiouracila , Proteínas/análise , Animais , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Colorimetria , DNA/análise , Modelos Animais de Doenças , Hidroxiprolina/análise , Hipotireoidismo/metabolismo , Masculino , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrofotometria , Tiroxina/biossíntese , Tiroxina/sangue , Tri-Iodotironina/biossíntese , Tri-Iodotironina/sangueRESUMO
O objetivo foi verificar a influência da deficiência dos hormônios tireoideanos induzida por propiltiouracil (PTU) na mucosa gengival do rato, analisando bioquimicamente as proteínas totais, colágeno (hidroxiprolina) e população celular (DNA). Foram utilizados 50 ratos machos da cepa Sprague-Dawley, separados em 2 grupos: propiltiouracil (PTU) (10 mg/d i.p.), e controle (C), durante 10 semanas. As proteínas totais foram determinadas pelo método de Lowry, a hidroxiprolina pelo método de Newman e DNA pelo método de Burton. Observou-se diminuição das proteínas totais no grupo PTU (PTU= 41,23 ± 24,05; C= 63,36 ± 18,05); não houve diferença na hidroxiprolina e DNA (PTU= 2,18 ± 1,48; C= 2,29 ± 1,51) e (PTU= 0,33 ± 0,19; C= 0,46 ± 0,31). Conclui-se que o tratamento com PTU diminui o conteúdo de proteínas totais na mucosa gengival do rato, provavelmente pela diminuição da síntese protéica, sem alteração do colágeno e da população celular.
This work aimed at verifying the influence of propilthiouracil (PTU)-induced thyroid hormone deficiency on gingival mucosa of young male rats, measuring total protein concentration, collagen content and DNA concentration as indices of cellular population. Fifty Sprague-Dawley rats were used. The animals were grouped in: PTU-treated (i.p. 10 mg/d) and control rats (C). The experience was maintained for a period of 10 weeks. Total protein content of gingival mucosa tissue was determined by the Lowry method; hydroxyprolin rate, as prototype aminoacid of collagen, was determined using the Newman method, and DNA concentration was measured by Burton's methodology. The results showed decreased amounts of PTU-treated rats gingival total protein content (PTU= 41.23 ± 24.05 vs. C= 63.36 ± 18.05); no alterations were seen in hydroxyprolin concentration neither in DNA content of PTU treated rats, respectively (PTU= 2.18 ± 1.48 vs. C= 2.29 ± 1.51) and (PTU= 0.33 ± 0.19 vs. C= 0.46 ± 0.41). Thus, PTU treatment promotes a decrease in total protein content of rat gingival mucosa that may be interpreted as a decrease in protein synthesis induced by the hypothyroid condition, but with no alteration either in collagen or nucleic acid rates.
Assuntos
Animais , Masculino , Ratos , Antitireóideos/farmacologia , Colágeno/análise , Gengiva/química , Hipotireoidismo/induzido quimicamente , Propiltiouracila/farmacologia , Proteínas/análise , Antitireóideos/metabolismo , Colorimetria , Colágeno/efeitos dos fármacos , Colágeno/metabolismo , Modelos Animais de Doenças , DNA , Hidroxiprolina/análise , Propiltiouracila/metabolismo , Proteínas/efeitos dos fármacos , Proteínas/metabolismo , Ratos Sprague-Dawley , Espectrofotometria , Tiroxina/biossíntese , Tiroxina/sangue , Tri-Iodotironina/biossíntese , Tri-Iodotironina/sangueRESUMO
Somatotrophic and thyroid hormones were determined around the onset of reproduction in broiler breeders reared in two different housing systems [dark, close-sided house (CH) and conventional, open-sided house (OH)]. In both groups age-related changes were obvious for thyroxine (T4), growth hormone (GH) and insulin-like growth factor (IGF-1); levels of T4 decreased, especially between 24 and 28 weeks in both groups; concomitantly GH sharply increased over the same period. A transient peak in triiodothyronine (T3) occurred between 25 and 27 weeks. The effect of housing was only present after the onset of lay. Between weeks 27-28 and the end of the period studied, the CH group showed higher levels of GH and T3 but lower T4 levels as compared to the OH group. A significant increase in GH after onset of lay, without any significant rise in T3 or in IGF-I, could point to a relative insensitivity to high plasma GH levels. Changes at GH receptor level, together with an increased pituitary GH secretion and/or decreased GH turnover may be expected. This may indicate that hypothalamo-pituitary changes at the onset of lay not only imply changes of gonadotrophic cell function, but also other hormonal axes. The relatively decrease in T4 without changes in T3, may point to a decrease in the activity of the thyrotropic axis.
Assuntos
Galinhas/sangue , Hormônio do Crescimento/sangue , Abrigo para Animais , Oviposição , Tiroxina/sangue , Tri-Iodotironina/sangue , Envelhecimento , Animais , Peso Corporal , Feminino , Hormônio do Crescimento/biossíntese , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/biossíntese , Luz , Maturidade Sexual , Tiroxina/biossíntese , Tri-Iodotironina/biossínteseRESUMO
The anterior pituitary contains abundant type II iodothyronine 5'-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.
Assuntos
Hipotireoidismo/enzimologia , Iodeto Peroxidase/metabolismo , Hipófise/citologia , Hipófise/enzimologia , Adaptação Fisiológica , Animais , Northern Blotting , Hipotireoidismo/patologia , Hipotireoidismo/fisiopatologia , Masculino , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Tiroxina/biossíntese , Tri-Iodotironina/biossíntese , Iodotironina Desiodinase Tipo IIRESUMO
Cutaneous manifestations of thyroid disease are protean in nature and affect all age groups. This review focuses on normal thyroid gland physiology, specific cutaneous/thyroid lesions such as the thyroglossal duct cyst and metastatic thyroid malignancies, nonspecific cutaneous alterations of the hyperthyroid and hypothyroid states, and the numerous associations of thyroid disease with other cutaneous and/or systemic disorders.