RESUMO
Hypothyroidism exerts deleterious effects on immunity, but the precise role of the hypothalamic-pituitary-thyroid (HPT) axis in immunoregulatory and tolerogenic programs is barely understood. Here, we investigated the mechanisms underlying hypothyroid-related immunosuppression by examining the regulatory role of components of the HPT axis. We first analyzed lymphocyte activity in mice overexpressing the TRH gene (Tg-Trh). T cells from Tg-Trh showed increased proliferation than wild-type (WT) euthyroid mice in response to polyclonal activation. The release of Th1 pro-inflammatory cytokines was also increased in Tg-Trh and TSH levels correlated with T-cell proliferation. To gain further mechanistic insights into hypothyroidism-related immunosuppression, we evaluated T-cell subpopulations in lymphoid tissues of hypothyroid and control mice. No differences were observed in CD3/CD19 or CD4/CD8 ratios between these strains. However, the frequency of regulatory T cells (Tregs) was significantly increased in hypothyroid mice, and not in Tg-Trh mice. Accordingly, in vitro Tregs differentiation was more pronounced in naïve T cells isolated from hypothyroid mice. Since Tregs overexpress galectin-1 (Gal-1) and mice lacking this lectin (Lgals1-/- ) show reduced Treg function, we investigated the involvement of this immunoregulatory lectin in the control of Tregs in settings of hypothyroidism. Increased T lymphocyte reactivity and reduced frequency of Tregs were found in hypothyroid Lgals1-/- mice when compared to hypothyroid WT animals. This effect was rescued by the addition of recombinant Gal-1. Finally, increased expression of Gal-1 was found in Tregs purified from hypothyroid WT mice compared with their euthyroid counterpart. Thus, a substantial increase in the frequency and activity of Gal-1-expressing Tregs underlies immunosuppression associated with hypothyroid conditions, with critical implications in immunopathology, metabolic disorders, and cancer.
Assuntos
Hipotireoidismo , Tireotropina , Camundongos , Animais , Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Linfócitos T Reguladores/metabolismo , Galectina 1/genética , Hipotireoidismo/metabolismo , Terapia de ImunossupressãoRESUMO
Thyrotropin-releasing hormone (TRH) and its receptors are expressed in the hypothalamus and limbic regions. Brain thyrotropin-releasing hormone actions are exerted directly through its receptors and indirectly by modulating the effects of neurotransmitters such as glutamate, gamma-aminobutyric acid, acetylcholine, and dopamine. The thyrotropin-releasing hormone has been implicated in eating and mood regulation. We integrate studies that analyze the role of limbic thyrotropin-releasing hormone on displaying depressive- and anxiety-like behaviors and anorexia or hyperphagia. Since the decade of 1970s, different efforts have been made to identify some of the thyrotropin-releasing hormone effects and its analogs in feeding regulation or to ameliorate symptoms in patients diagnosed with mood disorders, and to correlate anxious or depressive parameters with thyrotropin-releasing hormone levels in the cerebrospinal fluid or its expression in postmortem brain areas of affected patients. Pharmacological studies where the thyrotropin-releasing hormone is administered to animals by different routes and to distinct brain areas have elucidated its actions in behavioral changes of mood and feeding parameters. In addition, a variety of animal models of depression, anxiety, or anorexia and hyperphagia has suggested the association between the hypothalamic and limbic TRHergic system and the regulation of mood and feeding alterations. Different approaches employ the administration of anti-depressant, anxiolytic or anorectic agents to animals and describe changes in thyrotropin-releasing hormone content or expression in hypothalamic or limbic regions. The different effects on mood that result from modulating thyrotropin-releasing hormone expression may be beneficial to treat patients diagnosed with eating disorders.
Assuntos
Hipotálamo , Hormônio Liberador de Tireotropina , Animais , Ansiedade , Encéfalo/metabolismo , Humanos , Hipotálamo/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
Growth hormone (GH), together with thyroid hormones (TH), regulates growth and development, and has critical effects on vertebrate metabolism. In ectotherms, these physiological processes are strongly influenced by environmental temperature. In reptiles, however, little is known about the direct influences of this factor on the somatotropic and thyroid axes. Therefore, the aim of this study was to describe the effects of both acute (48h) and chronic (2weeks) exposure to sub-optimal temperatures (25 and 18°C) upon somatotropic and thyroid axis function of the green iguana, in comparison to the control temperature (30-35°C). We found a significant increase in GH release (2.0-fold at 25°C and 1.9-fold at 18°C) and GH mRNA expression (up to 3.7-fold), mainly under chronic exposure conditions. The serum concentration of insulin-like growth factor-I (IGF-I) was significantly greater after chronic exposure (18.5±2.3 at 25°C; 15.92±3.4 at 18°C; vs. 9.3±1.21ng/ml at 35°C), while hepatic IGF-I mRNA expression increased up to 6.8-fold. Somatotropic axis may be regulated, under acute conditions, by thyrotropin-releasing hormone (TRH) that significantly increased its hypothalamic concentration (1.45 times) and mRNA expression (0.9-fold above control), respectively; and somatostatin (mRNA expression increased 1.0-1.2 times above control); and under chronic treatment, by pituitary adenylate cyclase-activating peptide (PACAP mRNA expression was increased from 0.4 to 0.6 times). Also, it was shown that, under control conditions, injection of TRH stimulated a significant increase in circulating GH. On the other hand, while there was a significant rise in the hypothalamic content of TRH and its mRNA expression, this hormone did not appear to influence the thyroid axis activity, which showed a severe diminution in all conditions of cold exposure, as indicated by the decreases in thyrotropin (TSH) mRNA expression (up to one-eight of the control), serum T4 (from 11.6±1.09 to 5.3±0.58ng/ml, after 2weeks at 18°C) and T3 (from 0.87±0.09 to 0.05±0.01ng/ml, under chronic conditions at 25°C), and Type-2 deiodinase (D2) activity (from 992.5±224 to 213.6±26.4fmolI(125)T4/mgh). The reduction in thyroid activity correlates with the down-regulation of metabolism as suggested by the decrease in the serum glucose and free fatty acid levels. These changes apparently were independent of a possible stress response, at least under acute exposure to both temperatures and in chronic treatment to 25°C, since serum corticosterone had no significant changes in these conditions, while at chronic 18°C exposure, a slight increase (0.38 times above control) was found. Thus, these data suggest that the reptilian somatotropic and thyroid axes have differential responses to cold exposure, and that GH and TRH may play important roles associated to adaptation mechanisms that support temperature acclimation in the green iguana.
Assuntos
Hormônio do Crescimento/metabolismo , Iguanas/metabolismo , Temperatura , Glândula Tireoide/metabolismo , Hormônio Liberador de Tireotropina/metabolismo , Animais , Glicemia/análise , Corticosterona/sangue , Hormônio do Crescimento/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Iguanas/sangue , Iguanas/genética , Fator de Crescimento Insulin-Like I/genética , Iodeto Peroxidase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/sangue , Somatostatina/genética , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Tireotropina/genética , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/genética , Hormônio Liberador de Tireotropina/farmacologiaRESUMO
The thyrotropin-releasing hormone (TRH), an anorexigenic factor that reduces food intake in food-restricted animals, may be involved in motivation for food. Injected centrally, TRH impairs acquisition of food-rewarded behavior. Through the TRH-R1 receptors, TRH injected in the nucleus accumbens increases dopamine content-perhaps the mechanism by which the peptide modulates food motivation. This, however, is still to be demonstrated. We sought to evaluate dopamine release by microdialysis after a TRH injection into the nucleus accumbens shell in free-moving fasted rats. In addition, we assessed dopamine content and turnover by HPLC and the relationship with the motivation for food by analyzing the performance of rats during a progressive-ratio (PR) operant-conditioning test. Finally, we determined serum leptin and triiodothyronine (T3) levels in order to evaluate the animals' metabolic response to food restriction and the impact of intra-accumbal TRH administration on circulating hormones. Intra-accumbal injections of TRH reduced food intake in food-restricted rats-compared to counterparts treated with saline-, without further decreasing T3 or leptin levels, which dropped due to their dietary regime. TRH-injected rats had lower breaking points on the PR schedule, which indicated lower motivation to eat. Accordingly, compared to saline-treated animals, dopamine release and turnover increased in the nucleus accumbens of TRH-injected rats, a finding that suggests a relationship between motivation for food and TRH-induced release of dopamine.
Assuntos
Dopamina/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Motivação/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Análise de Variância , Animais , Condicionamento Operante/efeitos dos fármacos , Privação de Alimentos , Leptina/sangue , Masculino , Microdiálise , Núcleo Accumbens/metabolismo , Ratos , Ratos Wistar , Recompensa , Tri-Iodotironina/sangueRESUMO
Neurons of the paraventricular nuclei of the hypothalamus (PVN) that synthesize the peptide thyrotropin releasing hormone (TRH) control energy homeostasis. Identifying the circuits which regulate these neurons is critical to fully understand integration of metabolic information and the mechanisms that set thyroid hormone levels. We tested the hypothesis that nitric oxide (NO) acutely controls PVN TRH expression and thyrotropin (TSH) secretion by the anterior pituitary. The subcutaneous treatment of rats with N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthases, enhanced PVN TRH mRNA and medio-basal hypothalamic TRH levels, and reduced serum TSH concentration. Analysis of the effect of a NO donor in primary cultures of hypothalamic or anterior pituitary cells suggested that the effect of NO includes a direct action on hypothalamic neurons. The cold stress-induced increase in TSH release was inhibited by sc L-NAME. Therefore, production of NO may control the activity of the hypothalamus-pituitary-thyroid axis.
Assuntos
Temperatura Baixa , Óxido Nítrico/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , RNA Mensageiro/metabolismo , Estresse Fisiológico/fisiologia , Hormônio Liberador de Tireotropina/genética , Tireotropina/sangue , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/farmacologia , Radioimunoensaio/métodos , Ratos , Ratos Wistar , Estresse Fisiológico/efeitos dos fármacos , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Tri-Iodotironina/sangueRESUMO
Stimulation of the dorsal periaqueductal gray matter (DPAG) produces defensive behaviors which are reminiscent of panic attacks. Recent evidence from our laboratory showed that DPAG-evoked defensive behaviors are markedly attenuated in short-term methimazole-induced hypothyroidism. It is not clear, however, whether these effects were due to an increase in thyrotropin releasing hormone (TRH), a decrease in thyroid hormones or to the overall effects of hypothyroidism. Accordingly, here we examined whether the peripheral injection of TRH has any effect either on the panic-like behaviors induced by electrical stimulation of DPAG or anxiety-like behaviors of rats exposed to the elevated plus-maze (EPM). Rats whose stimulation of DPAG produced flight responses (galloping or jumping) with intensities below 60 microA were injected with 1 microg/kg TRH (i.p.) and stimulated 10min after that. The day after, rats were treated with saline and subjected to the same stimulation procedure. Threshold curves were fitted through the logistic model and compared by likelihood-ratio chi(2) tests. TRH and saline effects on EPM performance were appraised in separate groups. Compared to saline-sessions, TRH-injected rats presented thresholds significantly higher for immobility (40%), trotting (33%), galloping (34%), jumping (39%) and exophthalmus (43%). In contrast, TRH had no effects on EPM arm exploration. TRH selective inhibition of DPAG-evoked defensive behaviors adds new evidence that panic attacks may be attenuated by increased levels of this hormone in hypothyroidism.
Assuntos
Pânico/efeitos dos fármacos , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Reação de Congelamento Cataléptica/efeitos dos fármacos , Infusões Intravenosas , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Modelos Biológicos , Pânico/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Estimulação Física , Ratos , Ratos Wistar , Hormônio Liberador de Tireotropina/administração & dosagemRESUMO
Effects of a short-term hyper- and hypoprolactinaemia on serum concentrations of LH, testosterone and semen quality in six male Beagles were investigated. Blood samples were collected at 3-day intervals for 12 weeks. The time span was divided into five 3-week periods: pre-treatment, metoclopramide (MCP) treatment (0.2 mg/kg orally three times daily), cabergoline (CAB) treatment (5 microg/kg orally once daily), post-treatment 1 and post-treatment 2. In the latter, only semen characteristics were evaluated. Semen parameters were analyzed once per week during the whole 15-week investigation time. At the end of each period, the effects of a single intravenous injection of thyrotropin-releasing hormone (TRH; 10 microg/kg) on the secretion of prolactin (PRL), LH, testosterone, thyroid-stimulating hormone and thyroxine (T4) were investigated. Pre-treatment serum PRL concentration increased under MCP (p < 0.05), followed by a decrease under CAB administration (p < 0.05). Luteinizing hormone and testosterone concentrations were not affected. Except for straight-line sperm velocity, semen quality did not differ between collection periods. A single iv TRH injection induced a significant PRL increase at 20 min in all experimental periods except during CAB treatment. Luteinizing hormone and testosterone did not show clear TRH-related changes. Basic T4 levels were significantly reduced after CAB treatment (p < 0.05). The results of the present study demonstrate that MCP-induced short-term hyperprolactinaemia in male beagles does not seriously affect the hypothalamo-pituitary axis and semen quality.
Assuntos
Hipófise/efeitos dos fármacos , Prolactina/sangue , Sêmen/efeitos dos fármacos , Testículo/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Animais , Cabergolina , Cães , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Ergolinas/farmacologia , Hormônio Luteinizante/sangue , Masculino , Metoclopramida/farmacologia , Testosterona/sangue , Tireotropina/sangue , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologia , Tiroxina/sangueRESUMO
La búsqueda un método alternativo a la rh-TSH para estimular el aumento de la TSH sérica previo al tratamiento con 131I en pacientes con CDT operados con reducción del tiempo del hipotiroidismo pre ablativo fue el propósito del trabajo que iniciamos en el año 2001 en el Paraguay utilizando múltiples dosis de TRH para estimular la TSH endógena de los pacientes para luego lograr la ablación del remanente tiroideo con 131I. Se conoce que la inyección de una dosis única de 200µU de TRH por vía EV logra el aumento de la TSH endógena en los pacientes con carcinoma diferenciado de tiroides logrando elevar la TSH entre 30 - 35 mUI/L al final de la primera hora , sin embargo, no se cuentan con datos estadísticos de los efectos de múltiples inyecciones de TRH aplicadas por vía EV o por vía IM en los pacientes operados de tiroides por CDT previamente a la ablación con 131I. Material y Método: Desde el 2001al 2007 doscientos pacientes operados por CDT fueron estudiados por este método en el Centro de Diagnostico y Tratamiento Nuclear (CEDIN), 120 correspondieron a cáncer papilar y 80 a cáncer folicular. Ciento ochenta no presentaron metástasis a distancia y 20 presentaron metástasis en cuello, tórax, pelvis y columna dorsal. Tiroidectomía total se realizó en 120 y lobectomía total e itsmectomía más hemilobectomía del lado contra lateral en 80. Todos fueron tratados con dosis ablativas (100 mCi (3.700 mBq) de 131I excepto aquellos con metástasis que recibieron 150 mCi (5.500 mBq) previa estimulación con TRH por vía EV en dos dosis diarias por dos días con previa suspensión de L-tiroxina por 25 días antes del tratamiento reemplazándola por triyodotironina 25 mcg/día por 15 días tras lo cual también fue suspendida 10 días antes de la estimulación con TRH y el tratamiento con 131I. Dos pacientes con metástasis recibieron otra dosis extra de 150 mCi (5.550 MBq) 6 meses después...
The search of an alternative method to the rh-TSH to stimulate endogenous rising of TSH previous to thyroid ablation with 131I in patients with CDT operated. The purpose of the work began in 2001 in Paraguay using multiple dose of TRH IV (200µU of TRH Threlea® Argentina) to stimulate the own TSH of patients previous to 131I ablation. It is known that the injection of an unique dose of 200µU of TRH IV achieves the increasing of the endogenous TSH in patients with differentiated thyroid carcinoma up to 30 - 35 mUI/L at the end of the first hour, however, there is not statistical data of the effects of multiple injections of TRH applied IV or IM in operated patients of DTC previous to the ablation with 131I. Since 2001-2007, two hundred patients operated for DTC were studied by this method, 120 were papillary cancer and 80 follicular cancer. One hundred eighty did not have distance metastasis and 20 presented metastasis in thorax, pelvis and dorsal spine. Total thyroidectomy was carried out in 120 and total lobectomy with itsmectomy plus hemilobectomy of the other lobe in 80. All were treated with ablative dose of 100 mCi (3.700 mBq) of 131I, except those with metastasis which receive 150 mCi (5.500 mBq) with the previous stimulation with TRH IV with two daily dose for three days with previous suspension of L-tiroxine for 25 days and replaced by triyodotiroxine 25 mcg/d for 15 days with suspension 10 days before the stimulation with TRH and treatment with 131I. Two patients with metastasis received another extra dose of 150 mCi (5.550 MBq) 6 months later. One presented uptake in thyroid bed one year after the ablation received a new ablative dose of 100 mCi (3.700 mBq) of 131I. All the patients were interned and isolated by 48 hours. Twenty feminine patients had later pregnancies in 1-3 years after their ablative dose with healthy products. TSH was measured during the stimulation with TRH in all patients...
Assuntos
Humanos , Masculino , Feminino , Adenocarcinoma Folicular , Carcinoma Papilar , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/farmacologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Tireotropina , Fatores de Tempo , Grupos Controle , Injeções Intravenosas , Metástase Neoplásica/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo/uso terapêutico , Tireoglobulina/análise , Tireoglobulina , Tireotropina/análiseRESUMO
Objective: To characterize the thyroid function in mild (L), moderate (M), hemodialysis (HD), peritoneal dialysis (PD), chronic renal failure (CRE) and post kidney transplant (TX). Method: 46 children between 9.3 +/- 3.7 years-old with CRF (10 mild (L), 10 moderate (M), 10 peritoneodialysis (PD), 6 hemodialysis (HD), 10 transplants (TX)) were evaluated. Basal total T4 and free T3, TRH test (TSH at 0-30-60 min), creatinine, BUN, creatinine clearance and anthropometric parameters were measured. The statistics analysis included Anova Test to compare group results and correlation coefficients for studied variables. Results: Basal thyroid hormone levéis were normal in all groups and no differences between groups (except higher TSH in L (p < 0.01)) were found. TRH test response was prolonged on L, M, PD and HD and deficient in TX, except 3 TX patients who had normal TRH response, all using Tacrolimus, Micofenolate and Prednisone on altérnate day treatment versus the remaining TX who where on Cyclosporine or Azathioprine, Micofenolate and continuous corticoid régimen. Prolonged TRH response correlates with creatinine (p < 0.001) and creatinine clearance (p < 0,01). Conclusions: Basal thyroid hormones were normal in all groups. TRH test response was predominantly prolonged in L, M, PD and HD, suggesting adaptative phenomena at tertiary level, and correlates with renal function. TX patients had deficient TRH response, suggesting hypofisial dysfunction.
Objetivo: Caracterizar la función tiroidea y la respuesta a test de TRH (thyroid releasing hormone), en niños con enfermedad renal crónica (ERC) leve (L), moderada (M), peritoneodiálisis (PD), hemodiálisis (HD) y trasplantados renales (TX). Pacientes y Método: Se estudiaron 46 pacientes con ERC (10 L, 10 M, 10PD,6HDy 10TX),9,3 +/- 3,7 años. Se midió t4t,t41,t3t, t31,TBGbasalytest de TRH(TSHa 0,30y60min). Se evaluó función renal, antropometría y se consignó tratamiento inmunosupresor (IS) en el grupo TX. Se utilizó anova para comparar los resultados entre los grupos y coeficiente de correlación para las variables estudiadas. Resultados: Los valores basales de hormonas tiroideas fueron normales en todos los grupos, sólo TSH fue significativamente mayor en L aunque dentro del rango normal (p < 0,01). La respuesta al test de TRH fue predominantemente prolongada en L, M, PD y HD y deficiente en TX; los 3 pacientes TX con tacrolimus, micofenolato y prednisona en días alternos tuvieron respuesta normal a diferencia del resto TX que recibían prednisona continua, ciclosporina y micofenolato. La prolongación de respuesta a TRH se correlacionó con creatininemia, BUN y clearance de creatinina (p < 0,01). Conclusiones: Los niveles de hormonas tiroideas basales se encuentran normales en todos los grupos de ERC. La respuesta a TRH fue predominantemente prolongada en L, M, PD y HD, demostrando un fenómeno adaptativo a nivel terciario del eje hipotálamo-hipofisis-tiroides. Los TX presentan una respuesta mayoritoriamente deficiente a TRH, sugerente de disfunción hipofisiaria, la que podría estar relacionada con el tipo de tratamiento inmunosupresor y al uso de corticoides en días continuos.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina/farmacologia , Insuficiência Renal Crônica/fisiopatologia , Antropometria , Relação Dose-Resposta a Droga , Glândula Tireoide , Hormônios Tireóideos/sangue , Insuficiência Renal Crônica/sangue , Transplante de Rim , Estudos Prospectivos , Diálise Renal , Testes de Função TireóideaRESUMO
In humans, there is a significant decrease in serum T(3) and increase in rT(3) at different time points after myocardial infarction, whereas serum TSH and T(4) remain unaltered. We report here a time course study of pituitary-thyroid function and thyroid hormone metabolism in rats subjected to myocardial infarction by left coronary ligation (INF). INF- and sham-operated animals were followed by serial deiodination assays and thyroid function tests, just before, and 1, 4, 8, and 12 wk after surgery. At 4 and 12 wk after INF, liver type 1 deiodinase activity was significantly lower, confirming tissue hypothyroidism. Type 3 deiodinase (D3) activity was robustly induced 1 wk after INF only in the infarcted myocardium. Reminiscent of the consumptive hypothyroidism observed in patients with large D3-expressing tumors, this induction of cardiac D3 activity was associated with a decrease in both serum T(4) ( approximately 50% decrease) and T(3) (37% decrease), despite compensatory stimulation of the thyroid. Thyroid stimulation was documented by both hyperthyrotropinemia and radioiodine uptake. Serum TSH increased by 4.3-fold in the first and 3.1-fold in the fourth weeks (P < 0.01), returning to the basal levels thereafter. Thyroid sodium/iodide-symporter function increased 1 wk after INF, accompanying the increased serum TSH. We conclude that the acute decrease in serum T(4) and T(3) after INF is due to increased thyroid hormone catabolism from ectopic D3 expression in the heart.