Evidence of the Presence of Thyroid Hormones in Achatina fulica Snails

ABSTRACT The objective of this study was to identify thyroid hormones and to examine their putative site of synthesis in Achatina fulica snails. For this purpose, radioimmunoassays were performed for T3 and T4 before and after long starvation with or without hemolymph deproteinization. Sodium/iodide symporter activity in vivo was analyzed through 125I administration with and without KClO4 pretreatment. Only T4 was detected, and its concentration decreased due to starvation or deproteinization. However, high-performance liquid chromatography analysis also showed the presence of T2 and T3 apart from T4, but rT3 was not detected in the A. fulica hemolymph. The sodium/iodide symporter activity was greater in cerebral ganglia than digestive gland, but KClO4 treatment did not inhibit iodide uptake in any of the tissues analyzed. Altogether, our data confirm for the first time the presence of thyroid hormones in A. fulica snails and suggest their participation in the metabolism control in this species, although the putative site of hormone biosynthesis remains to be elucidated.

Effects of excess maternal thyroxin on the bones of rat offspring from birth to the post-weaning period

ABSTRACT Objective To evaluate, in rat offspring, bone changes induced by excess maternal thyroxin during pregnancy and lactation, and to assess the reversibility of these changes after weaning. Material and methods Twenty Wistar rats were distributed in two groups, hyperthyroid and control, that were treated daily with L-thyroxin (50 mcg/animal) and placebo, respectively. The treatment was initiated seven days before mating and continued throughout pregnancy and lactation. From every female of each of the two groups, two offspring were euthanized after birth, two at 21 days of age (weaning), and two at 42 days of age (21 days after weaning). In newborns, the length of pelvic and thoracic limbs were measured, and in the other animals, the length and width of the femur and humerus were measured. Bones were dissected, decalcified, embedded in paraffin, and analyzed histomorphometrically. Results Excess maternal thyroxin significantly reduced the length of the pelvic limb in neonates. In 21-day-old individuals, excess maternal thyroxine reduced the length and the width of the femur and the humerus. It also increased thickness of the epiphyseal plate and the percentage of trabecular bone tissue. In 42-day-old individuals, there were no significant differences between groups in relation to the parameters evaluated in the previous periods. Conclusion Excess maternal thyroxine reduced growth in suckling rats both at birth and at weaning, and it also increased the percentage of trabecular bone tissue in 21-day-old animals. These changes, however, were reversible at 42 days, i.e., 21 days after weaning. Arch Endocrinol Metab. 2016;60(2):130-7.

Effects of magnesium on cytomorphology and enzyme activities in thyroid of rats.

Till date knowledge regarding the effects of high dietary magnesium on thyroid gland is incomprehensive though certain epidemiological studies reported development of thyroid gland dysfunctions in people with chronic exposure to hard water (especially with high magnesium) despite sufficient iodine consumption. The present study is to explore the effects of chronic high dietary magnesium exposure on thyroid morphology and functional status. Male adult albino Wistar strain rats were treated with graded doses of magnesium sulphate (MgSO4; 0.5, 1.0 and 1.5 g %) for 60 days and changes in different thyroid parameters were investigated. Significantly stimulated thyroid peroxidase and Na+–K+-ATPase and altered idothyronine 5/- deiodinase type I activities, enhanced serum thyroxine (T4) (both total and free), total triiodothyronine (T3) and thyroid stimulating hormone with decreased free T3 levels and T3/T4 ratio (T3:T4) along with enlargement of thyroid with associated histopathological changes were observed in the treated groups. The results clearly confirm that chronic high dietary magnesium exposure causes potential thyroid disruption as reported in earlier epidemiological studies.

The multiple effects of thyroid disorders on bone and mineral metabolism / Os múltiplos efeitos das disfunções tireoidianas sobre o metabolismo osteomineral

Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.

Diferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT.

Central hypothyroidism.

A 15-mth-old male child of consanguineous parents, presented with classical features of congenital hypothyroidism. Serum total thyroxine (T4), total triiodothyronine (T3) and TSH were low. There was no evidence of deficiency of other pituitary hormones. Magnetic resonance imaging of the pituitary was normal. TSHB gene sequencing revealed a homozygous missense mutation due to single base substitution G?A at codon 85 resulting in change from Glycine to Arginine. This mutation in TSHB gene has been reported earlier in three cases with similar phenotype from Japan.

The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism: [review] / O paciente difícil: interação entre drogas e influência de doenças concomitantes no tratamento do hipotiroidismo: [revisão]

Although most hypothyroid patients do well with one single tablet of thyroxine daily, approximately 10 percent are dissatisfied and another important group of patients is difficult to control. We reviewed the most common causes for frequent-dose adjustment or high-dose requirement, including poor compliance with therapy and inadequate medication. Since these two causes have been ruled out, drug interaction and other concomitant diseases need to be investigated. Requirements of thyroxine increase in all conditions characterized by impaired gastric acid secretion. Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption. In addition, a series of diseases including celiac disease and chronic inflammatory intestinal diseases, as well as nutritional habits may be important in patient control. Finally, we mention the effects of a growing list of drugs and thyroid disruptors that may also affect thyroid hormone metabolism at many levels.

Embora a maior parte dos pacientes com hipotiroidismo fique bem com um único comprimido diário de tiroxina, aproximadamente 10 por cento não ficam satisfeitos e outro importante grupo de pacientes apresenta controle difícil. Foram revistas as causas mais comuns para necessidades frequentes de ajuste de dose ou uso de dose elevadas, incluindo falta de adesão à terapia e medicação inadequada. Descartando-se essas duas causas, é necessário investigar o uso de drogas e a presença de doenças concomitantes. Existe necessidade maior de tiroxina quando diminui a secreção ácida do estômago. Inibidores de bomba de prótons, antiácidos e uma longa lista de drogas podem dificultar a absorção da tiroxina. Várias doenças, incluindo a doença celíaca e as doenças intestinais inflamatórias crônicas, além dos hábitos alimentares, são importantes no controle do paciente hipotiroideo. Finalmente, foram mencionados os efeitos de uma lista crescente de drogas e disruptores que podem afetar o metabolismo tiroidiano em diferentes níveis.

Concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4) em bodes submetidos ao estresse calórico / Plasma concentrations of testosterone, triiodothyronine (T3), and thyroxine (T4) in bucks submitted to heat stress

Para verificar o efeito do estresse calórico (EC) nas concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4), oito bodes, das raças Saanen (n=4) e Alpina (n=4), foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC) durante 30 dias e, após um período (60 dias) de descanso, submetidos ao EC (23,7ºC a 34,0ºC) por 30 dias. Para minimizar as variações sazonais nos perfis hormonais devido ao fotoperíodo, durante toda fase experimental, incluindo a de adaptação em condições de termoneutralidade (30 dias), o fotoperíodo foi controlado utilizando-se alternância de dias longos (16h de luz e 8h de escuro) e de dias curtos (8h de luz e 16h de escuro) a cada 30 dias. As amostras de sangue foram coletadas duas vezes por semana durante cinco semanas. No conjunto das raças, o EC não influenciou (P>0,05) as concentrações de testosterona (1,8±0,2 vs 1,3±0,2ng/ml) e nem a de T4 (52,7±2,8 vs 50,0±2,8ng/ml). Houve declínio (P<0,01) das concentrações de T3 nos animais submetidos ao experimento (1,3±0,1 vs 1,0±0,1ng/ml), mas a redução foi observada somente nos bodes Saanen. Em ambas as raças, as concentrações de T3 e T4 variaram (P<0,01) conforme o dia da coleta das amostras de sangue. O EC foi suficiente para produzir uma resposta fisiológica com redução das concentrações plasmáticas de T3 em bodes das raças Saanen, mas não da raça Alpina, assim como não foi capaz de alterar os níveis plasmáticos de testosterona e nem de T4.

To verify the effect of heat stress (HS) on plasma testosterone, triiodothyronine (T3), and thyroxine (T4) concentrations, eight Saanen (n=4) and Alpine Brown (n=4) bucks were kept in climate chamber under thermal neutral conditions (13.0ºC to 26.7ºC) for 30 days. After a resting period (60 days), the same bucks were submitted to heat stress (23.7ºC to 34.0ºC) for another 30 days. To neutralize the seasonal variations of hormonal profiles throughout the period, the photoperiod was controlled every 30 days altering long (16 hours of light and 8 hours of darkness) and short days (8 hours of light and 16 hours of darkness). The blood samples were collected twice a week during five weeks. In both breeds, there was no effect of HS (P>0.05) on plasma concentrations of testosterone (1.8±0.2 vs 1.3±0.2ng/ml) and T4 (52.7±2.8 vs 50.0±2.8ng/ml). There was a decline (P<0.01) of plasma T3 concentrations (1.3±0.1 vs 1.0±0.1ng/ml) after HS treatment, but this reduction was only evident in Saanen bucks. In both breeds, the plasma concentrations of T3 and T4 varied (P<0.01) according to the day of blood sample collection. The HS was sufficient to provoke a physiological response with reduction of plasma concentrations of thyroid hormones mainly of T3 in Saanen bucks, but not in Alpine ones. The HS did not affect the plasma testosterone and T4 levels.

Impacto do tratamento com GH sobre as funções tireoidiana e adrenal: [revisão] / hGH treatment impact on adrenal and thyroid functions: [review]

O estado somatotrófico é modulador importante dos eixos tirotrófico e corticotrófico. Enquanto a reposição somatotrófica em pacientes com deficiência de GH aumenta a conversão do hormônio inativo (T4) na sua forma ativa (T3), aumentando dessa forma a ação biológica do hormônio tireoidiano, a mesma reposição induz no eixo corticotrófico a conversão de cortisol, hormonalmente ativo, em cortisona, que é biologicamente inativa. Nessa revisão, foram discutidos os efeitos do GH nesses dois eixos hormonais, os possíveis mecanismos e as implicações clínicas no manejo dos pacientes com hipopituitarismo.

Somatotrophic status is a major determinant of both thyrotrophic and corticotrophic axis. In growth hormone deficient patients, somatotrophic replacement increases the conversion rate of the inactive form of the thyroid hormone (T4) to its active form (T3), whereas the same replacement induces the conversion of cortisol, which is hormonally active, in cortisone, its inactive form. This review details the effects of GH on these two hormonal axis, possible mechanisms and clinical implications for the management of hypopituitary patients.

Expressão das iodotironinas desiodases nas neoplasias tireoidianas / Iodothyronine deiodinases expression in thyroid neoplasias

As iodotironinas desiodases formam uma família de selenoenzimas com propriedades catalíticas distintas que ativam ou inativam os hormônios tireoidianos via desiodação do anel fenólico ou tirosínico da molécula do T4. As desiodases tipo I e II (D1 e D2) são as enzimas responsáveis pela geração do T3 e são amplamente expressas na tireóide normal. A transformação neoplásica benigna ou maligna da glândula tireóide está associada a alterações na expressão dessas isoenzimas, sugerindo um possível papel da D1 e da D2 como marcadores de diferenciação celular. Anormalidades na expressão de ambas enzimas e da desiodase tipo III (D3), inativadora do hormônios tireoidianos, são também encontradas em outras neoplasias humanas. Os mecanismos ou implicações do aumento ou diminuição das desiodases na patogênese neoplásica são pouco compreendidas. No entanto, é importante observar que a expressão anormal da D2 pode ser responsável por um quadro de tireotoxicose em pacientes com metástases de carcinoma folicular de tireóide, enquanto que o aumento da D3 em hemangiomas pode causar hipotireoidismo de difícil tratamento.

The iodothyronine deiodinases constitute a family of selenoenzymes that catalyze the removal of iodine from the outer ring or inner ring of the thyroid hormones. The activating enzymes, deiodinases type I (D1) and type II (D2), are highly expressed in normal thyroid gland. Benign or malignant neoplastic transformation of the thyroid cells is associated with changes on the expression of these enzymes, suggesting that D1 or D2 can be markers of cellular differentiation. Abnormalities on the expression of both enzymes and also of the deiodinase type III (D3), that inactivates thyroid hormones, have been found in other human neoplasias. So far, the mechanism or implications of these findings on tumor pathogenesis are not well understood. Nevertheless, its noteworthy that abnormal expression of D2 can cause thyrotoxicosis in patients with metastasis of follicular thyroid carcinoma and that increased D3 expression in large hemangiomas causes severe hypothyroidism.

A relação entre a função tireoidiana e a depressão: uma revisão / The relation between thyroid function and depression: a review

OBJETIVO: O papel da função tireoidiana nas doenças depressivas é pouco claro. Embora existam algumas evidências de que discretas alterações tireoidianas predisponham a casos de depressão, as anormalidades específicas envolvendo a tireóide e os quadros depressivos permanecem pouco conhecidas. Serão destacados nesta revisão os principais achados envolvendo os quadros depressivos e a função tireoidiana, com especial atenção na participação das monoaminas cerebrais nesta relação. MÉTODO: Foram realizados levantamento no sistema Medline e na literatura. RESULTADOS: Existem evidências de atividade alterada do eixo hipotálamo-hipófise-tireóide (HHT) em alguns casos de depressão, que incluem: aumento dos níveis de T4, resposta alterada do TSH pós-estímulo com TRH, presença de anticorpos antitireoidianos e concentração elevada de TRH no LCR. A relação entre estas anormalidades, as principais monoaminas cerebrais e os subtipos de quadros depressivos é complexa e ainda não permite o estabelecimento de hipóteses diretas de compreensão. CONCLUSÕES: Após anos de pesquisas, permanece pouco esclarecida a importância da relação entre o eixo HHT e as depressões, assim como os mecanismos subjacentes às alterações tireoidianas encontradas nos pacientes deprimidos. Portanto, mais pesquisas serão necessárias para uma melhor compreensão do papel do eixo HHT na patogênese e no tratamento dos quadros depressivos.

Thyroid functions in pre-eclampsia and its correlation with maternal age, parity, severity of blood pressure and serum albumin.

Maternal thyroid function was investigated in 32 pre-eclamptic women and 10 normal pregnant women in their third trimester. Serum total tri-iodothyronine (TT3) and total thyroxine (TT4) were decreased significantly (P < 0.001) and TSH was increased significantly (P < .001) in pre-eclampsia as compared to normal pregnancy. There was no influence of parity and maternal age on thyroid functions. TT3 and TT4 decreased significantly (P < .001) with increase of serum albumin, while there was no correlation of TT4 with serum albumin.

Hipertiroxinemia con eutiroidismo clínico: análisis a propósito de un caso / Hyperthyroxinemia and clinical euthyroidism: report of one case

The association of hyperthyroxinemia and euthyroidism is frequent and characterized by high plasma thyroxin concentrations, normal TSH values and absence of clinical signs of hyperthyroidism. We report an asymptomatic 28 years old male presenting with a serum total plasma thyroxin of 18.5 µg/dl (N 6.1-12.5), a free thyroxin of 2.9 ng/dl (N 0.8-1.4), a TSH of 3.4 µIU/ml (N 0.5-5), and a triiodothyronine of 128 ng/dl (N 80-180). Laboratory assessment did not find high thyroxin binding globulin, albumin or prealbumin concentrations or antithyroxin antibodies. The thyroxin binding capacity of albumin was elevated to 58.2 µg/dl (N 11.5-34.1). TSH responded normally to TRH stimulus and was suppressed with exogenous triiodothyronine, which caused an hyperthyroid syndrome. We concluded that this patient had a familial dysalbuminemia

El cinc inhibe la conversion de tiroxina en triidotironina en grasa parda in vitro / Zinc inhibits the in vitro conversion of thyroxine to triidothyronine in brown adipose tissue

Se estudió el efecto del cinc sobre la conversión de tiroxina (T4) a triodotironina (T3) en homogenatos de grasa parda de ratas expuestas a temperaturas de 4 grados Celsius o 22 grados Celsius durante 24 h. Luego de sacrificar a los animales por dislocación cervical, se extrajo la grasa parda interescapular y se homogeneizó en buffer sacarosa (320 mM) y HEPES (10 mH) pH 7.4. Se centrifugó el preparado a 4 grados Celsius y se separó la capa que contiene la actividad 5'-deiodinasa. Se separaron alícuotas a las que se agregaron 50, 100 muM, 1 o 5 mM sulfato de cinc, más 0.5, 10 o 25 mM ditiotreitol (DTT) y 1 muCi (125)I-T4. El preparo se incubó a 37 grados Celsius durante 60 min luego de lo cual se hizo cromatografía en papel para separar los diferentes compuestos radioactivos del homogenato. En ratas mantenidas a 22 grados Celsius, la deiodinación de T4 produjo 13.3 por ciento de T3, equivalente a 79 + 30 pg/mg proteina/h. Las dosis de 1 y 5 mM cinc inhibieron significativamente la producción de T3, En ratas expuestas a 4 grados Celsius, la producción basal de T3 se incrementó a 248 + 37 pg/mg proteina/h. Al agregar cinc en dosis de 100 muM, 1 o 5 mM, se redujo significativamente la deiodinación de T4. La acción inhibidora del sinc sobre la producción de T3 en la grasa parda tendría efectos deletéreos sobre la termogénesis en ese tejido.

Changes induced by zinc on thyroxine deiodination by rat liver in vivo and in vitro

Se estudió el efecto de la administración in vivo o del agregado in vitro de zinc sobre la deiodinación 5'de la tiroxina (T4) por el hígado de rata y sobre la concentración hepática de grupos sulfhidrilos libres (NPSH). Se usaron ratas Wistar macho de 200-240g de peso corporal. A un grupo de 12 ratas se les inyectó i.p. sulfato de zinc 2mg/Kg de peso, 24h antes de iniciar el estudio. Se sacrificaron los animales por dislocación cervical y el hígado fue inmediatamente homogeneizado. Se agregó a los homogenatos dithithreitol (DTT) (0,2.5,5 o 10mM concentración final) y 1µCi de 125I-T4. Para los estudios in vitro en animales sin tratar, se agregó al homogenato de hígado sulfato de zinc o cloruro de cadmio (2.5 o 5mM) más DTT y T4 marcada. Todos los homogenatos fueron incubados durante 90 min a 37ºC y luego cromatografiados en papel Whatman 1. Las ratas inyectadas con zinc tuvieron una disminución significativa (p<0.01) de la deiodinación de T4, de la producción de 125 iodo (P<0.02) y de triiodotironina (T3) (P<0.05). En los estudios in vitro, el agregado de zinc o cadmio disminuyó significativamente la degradación de T4 (P<0.02) y la producción de iodo (P<0.02 para el zinc y P<0.05 para el cadmio) y de T3 (P<0.05). La concentración hepática de NPSH en los animales inyectados con zinc fue normal. La concentración sérica de T4 y T3 en los animales inyectados con zinc fue normal pero en los inyectados con cadmio se redujo significativamente (P<0.01 para T4 y P<0.02 para T3). Los resultados indican que el zinc inhibe la actividad de la 5'-deioidnasa hepática, por um mecanismo probablemente relacionado con la unión del metal a los grupos sulfhidrilos de la enzima

Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat.

Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT.

Efecto de la amiodarona sobre la conversión de tiroxina a triiodotironina en el miocardio de la rata in vivo e in vitro / Effect of amiodarone on the conversion of thyroxine to triiodothyronine in rat myocardium

El presente trabajo estudió la conversión de titoxina (T4) a triiodotironina (T3) en el miocardio e hígado de ratas tratadas con la droga antiarrítmica amiodarona. Ratas Wistar de 200 g de peso fueron inyectadas con amiodarona 2,5 mg/100 g de peso, ip, diariamente durante 12 días, o con la droga inhibidora de la deiodinación de T4, el ácido iopanoico (IOP) 5 mg/100 g de peso, ip, cada 12 horas durante 72 horas. Posteriormente, el corazón e hígado de cada animal fueron homogeneizados en buffer Krebs-Ringer fosfato, pH 7,4 (1:4). Alíucotas de 400 micronl de homogenato fueron separadas y se agregó ditiotreitol 8 mM y 10**-2 micronCi de 125I-T3. Para los estudios in vitro de animales no trtados, se agregó a los homogenatos, además, amiodarona 0,1 mM o IOP 10 mM. Los viales se incubaron por 2 horas a 37-C y se hizo cromatografía en alcohol amílico terciario: hexano: amonio (5:1:6). La producción de T3 en el miocardio e hígado de los grupos tratados con amiodarona o IOP descendió significativamente respecto de los controles, mientras que en los estudios in vitro la amiodarona no tuvo efecto sobre la deiodinación de T4 y el IOP bajó significativamente la conversión de T4 a T3. La degradación de T3 no fue alterada por ninguna de las dos drogas en ninguno de los dos tejidos. La amiodarona descendió signifcativamente la tirotrofina y la T3 séricas, mientras que aumentó significativamente la T4 sérica. el IOP tuvo el mismo efecto sobre la T4 y T3, pero aumentó significativamente la TSH circulante. Se concluye que el bloqueo de la producción miocárdica de T3 inducido por la amiodarona no sería el responsable de su acción antiarrítmica