Survival of teleost larvae requires growth and development which depend upon endocrine processes. In this dissertation I have examined the ontogeny of elements of the thyroid hormone (TH) and corticosteroid (CS) systems in red drum (Sciaenops ocellatus). Basal cortisol production was first detected 3 days post-hatch (DPH) and a cortisol stress response was present from 6 DPH forward. Changes in steroidogenic enzyme mRNA (CYP11B and CYP21) levels did not correlate with these events. The time necessary to reach peak cortisol levels as well as return to basal levels declined as larvae developed. A second set of studies examined ontogenetic patterns in levels of mRNAs encoding thyroid (soTR[alpha] and soTR[beta]) and corticosteroid (soGR) hormone receptors and assessed the regulation of these mRNAs by exogenous triiodothyronine (T3) and cortisol. soTR[alpha], soTR[beta] and soGR were expressed in all stages of red drum examined. soTR[alpha] levels increased during the time when surging TH levels have been reported. soTR[beta] levels did not differ significantly during development. soGR levels were strongly correlated with those of soTR[alpha]. T3 up-regulated soTR[alpha] and soTR[beta] levels in 7 DPH, but not older larvae. Cross-regulation of receptor mRNAs by exogenous treatment with T3 or cortisol was not observed. Finally, I assessed the influence of a common herbicide, atrazine, on receptor mRNA, TH levels and growth of red drum. In two experiments, red drum exposed to environmentally relevant levels of atrazine did not alter hormone receptor mRNA levels, or TH content. However, atrazine did depress growth in some instances. In conclusion, the expression patterns of hormone receptor mRNA in embryos suggests receptor proteins could be activated by maternal hormones prior to the onset of endogenous hormone production. A correlation between soTR[alpha] and soGR mRNA levels suggests coordinated function of TH and CS systems, although regulatory interactions between these systems were not evident under the conditions in this study. Patterns in soTR[alpha] and soTR[beta] mRNA levels support an important role for TH in the larval to juvenile transformation of red drum larvae. The results also support growing evidence indicating atrazine exposure effects larval growth and may impact their survival in the wild. / text

Psychosocial factors affect the occurrence of coronary artery disease (CAD) disease and development of complications. People with depression or anxiety symptoms have the activate hypothalamic-pituitary-adrenal axis. Thyroid hormone changes are also found in patients with CAD. Fatigue and health-related quality of life (HRQoL) depends not only on good physical health, but also on psychoemotional state, especially on the presence of depression and anxiety disorders. Therefore, it is important to evaluate complex of hormonal markers and behavioral factors (depression, anxiety and fatigue) interaction on patients with CAD for quality of life, disease course and outcome. The aim of this study was examine relationship of cortisol and thyroid axis hormones concentrations with NT-pro B type natriuretic peptide (NT-proBNP) concentrations and with patient oriented outcomes such as depressive symptoms, fatigue and HRQoL in CAD patients. Study demonstrates relationship between thyroid axis hormones and cortisol concentrations with depression, anxiety symptoms, fatigue and HRQoL in CAD patients. Low T3, free T4 and higher RT3 concentrations are associated with higher NT-proBNP levels, depression symptoms, higher fatigue and worse HRQoL. Higher morning cortisol concentrations are associated with depression symptoms in women. The data obtained can be used in patients with coronary artery disease and depressive anxiety disorder, disease progression, and prognosis and quality of life... [to full text] / Psichosocialiniai veiksniai turi įtakos išeminės širdies ligos (IŠL) vystymuisi ir komplikacijų atsiradimui. Depresijos ir nerimo patogenezėje dalyvauja pagumburio-hipofizės-antinksčių ašis. Skydliaukės hormonų pokyčiai taip pat dažnai randami sergantiesiems IŠL bei depresija. Nuovargis ir su sveikata susijusi gyvenimo kokybė priklauso ne tik nuo geros fizinės sveikatos, bet ir nuo psichoemocinės būklės, todėl svarbu kompleksiškai įvertinti hormoninių žymenų ir elgesio veiksnių (depresijos, nerimo ir nuovargio) sąveikos įtaką sergančiųjų IŠL gyvenimo kokybei, ligos eigai bei baigtims. Šio tyrimo tikslas buvo išnagrinėti kortizolio ir skydliaukės ašies hormonų koncentracijų ryšį sergantiesiems IŠL su N-galinio smegenų tipo natriuretinio propeptido (NT-proBNP) koncentracija bei subjektyviomis sveikatos būklėmis: depresijos, nerimo simptomais, nuovargiu ir su sveikata susijusia gyvenimo kokybe. Tyrimas parodė skydliaukės hormonų ir kortizolio koncentracijų reikšmingą ryšį su subjektyviu sveikatos vertinimu sergantiesiems IŠL. Mažesnė bendrojo T3, laisvojo T4 ir didesnė reversinio T3 koncentracija susijusi su didesne NT-proBNP koncentracija, depresijos simptomų pasireiškimu, didesniu nuovargiu ir blogesniu su sveikata susijusios gyvenimo kokybės vertinimu. Didesnė rytinio kortizolio koncentracija susijusi su depresijos simptomų pasireiškimu moterims. Gauti duomenys gali būti panaudoti sergančiųjų IŠL depresijos bei nerimo simptomams, ligos eigai, prognozei ir gyvenimo kokybei... [toliau žr. visą tekstą]

Dissertation (Ph.D.)--University of South Florida, 2009. / Includes vita. Includes bibliographical references. Also available online.

Objetivo: Descrever características biológicas e ambientais associadas a habilidades motoras finas, medidas por diferentes níveis de conduta visual em lactentes de 1 e 3 meses. Desenho de estudo: 82 díades mãe-bebê foram recrutadas durante consultas pré-natais ou imediatamente após o nascimento e visitadas duas vezes para a coleta de dados (25-40 e 85-100 dias após o nascimento). Durante as visitas foram coletados fatores maternos (idade materna, escolaridade, tipo de parto, número de consultas pré-natais, tipo de amamentação e tabagismo), características biológicas do bebê (gênero, idade gestacional, nascimento, peso, circunferência da cabeça, Apgar), testes motores infantis (através da Escala de Avaliação do Comportamento Visuomotor Infantil e Alberta Infant Motor Scale/AIMS), perfil psicológico materno (através da Escala de Depressão Pós-natal de Edimburgo/EPDS e Escala de Ansiedade de Hamilton), variáveis ambientais (medidas pelo Affordance in the home environment for development scale/AHEMD), cuidados maternos (avaliado através do Coding Interacting Behavior/CIB), bem como a coleta de leite (medição de ácidos graxos totais, proteínas e cortisol) e sangue materno (medição de hormônios séricos e interleucinas). Resultados: 51 crianças foram testadas em tarefas de conduta visual e outras medidas. As mães das crianças com baixos escores de fixação visual apresentaram maiores níveis de proteína no leite materno aos 3 meses. Quanto ao perfil metabólico materno, as mães das crianças que apresentaram melhores escores de fixação visual apresentaram melhores níveis séricos de T4 (no primeiro mês) e prolactina (no terceiro mês). Conclusão: O desenvolvimento neuromotor precoce do bebê, especialmente as habilidades visuais e de motricidade fina, estão intimamente associados aos fatores biológicos maternos (fatores metabólicos maternos e composição do leite materno). / Objective: To describe biological and environmental characteristics associated with fine motor skills measured by different levels of visual tracking in infants of 1 and 3 months. Study design: 82 mother-infant dyads were recruited during prenatal consultations or immediately after birth and visited at two times for data collection (25-40 and 85-100 days after birth). During the visits were collected maternal factors (maternal age, education level, type of delivery, number of antenatal consultations, type of breastfeeding and smoking), biological characteristics of the baby (gender, gestational age, birth, weight, head circumference, Apgar), infant motor tests (through the Child Visuomotor Behavior Rating Scales and Alberta Infant Motor Scale/AIMS), maternal psychological profile (through the Edinburgh Postnatal Depression Scale/EPDS and Hamilton Anxiety Scale), environmental variables (measured by the Affordance in the home environment for development scale/AHEMD), maternal care (evaluated through Coding Interacting Behavior/CIB), as well as milk collection (measurement of total fatty acids, proteins and cortisol) and maternal blood (measurement of serum hormones and interleukins). Results: 51 children were tested on visual tracking tasks and other measures. The mothers of children with low visual fixation scores presented higher levels of protein in breastmilk at 3 months. Regarding the maternal metabolic profile, the mothers of the children who presented better visual conduct scores had better serum levels of T4 (in the first month) and prolactin (in the third month). Conclusion: Early neuromotor development of the baby, especially the visual and fine motor skills, are closely associated with maternal biological characteristics (metabolic factors and composition of breast milk).

Chez les hamsters, les jours longs activent la reproduction. Cette activation photopériodique (AP) impliquerait la mélatonine, l’hormone thyroïdienne (HT) et les RFamides hypothalamiques. Si les jours courts inhibiteurs sont maintenus au-delà de 20 semaines, une réactivation photoréfractaire (RP) de l’axe hypothalamo pituitaire gonadotrope (HPG) est déclenchée. Les mécanismes de cette RP sont inconnus. Notre analyse de la cinétique des changements moléculaires induits par l’AP et la RP montre dans les deux cas une inhibition précoce de l’expression de la Désiodinase 3 (Dio3), l’enzyme catabolisant les HT, dans les tanycytes. Associée à une inhibition tardive du transporteur MCT8 des HT, la diminution de Dio3 pourrait créer un pic d’HT dans l’hypothalamus. Dans les 2 activations, Kisspeptine et RFRP3 augmentent plusieurs semaines après l’inhibition de Dio3 et l’activation de l’HPG. Aussi, une inhibition d’RFRP3 lors de l’AP n’affecte pas l’HPG, mettant en cause le rôle du RFRP3. Nous avons donc découvert une inhibition précoce de Dio3 pouvant induire l’activation saisonnière de l’HPG. Le régulateur saisonnier précoce de Dio3 reste à découvrir. / In hamsters, reproduction is activated by long days. This photoactivation (PA) supposedly involves melatonin, hypothalamic thyroid hormones (TH) and RFamide peptides. Maintaining inhibitory short days for over 20 weeks triggers a photorefractory reactivation of the hypothalamo pituito gonadotropic axis (HPG) The mechanisms of this PR are so far unknown. Our cinetic analysis of the dynamic molecular changes in PA and PR revealed a conserved early inhibition of tanycytic deiodinase 3 (Dio3), which catabolizes TH, in both activation mechanisms. Associated with a late decrease of the TH transporter MCT8, the inhibition of Dio3 could generate an early peak of hypothalamic TH. In both activations, RFamide upregulation occurs several weeks after the initial Dio3 inhibition. Also, pharmacological inhibition of RFRP3 during PA does not influence the HPG activity, questioning the role of RFRP3 in HPG activation. We have thus uncovered a so far unreported early Dio3 inhibition that could be sufficient to seasonally reactivate the gonadotropic axis. The seasonal regulator of Dio3 remains to be discovered.

Objetivo: Descrever características biológicas e ambientais associadas a habilidades motoras finas, medidas por diferentes níveis de conduta visual em lactentes de 1 e 3 meses. Desenho de estudo: 82 díades mãe-bebê foram recrutadas durante consultas pré-natais ou imediatamente após o nascimento e visitadas duas vezes para a coleta de dados (25-40 e 85-100 dias após o nascimento). Durante as visitas foram coletados fatores maternos (idade materna, escolaridade, tipo de parto, número de consultas pré-natais, tipo de amamentação e tabagismo), características biológicas do bebê (gênero, idade gestacional, nascimento, peso, circunferência da cabeça, Apgar), testes motores infantis (através da Escala de Avaliação do Comportamento Visuomotor Infantil e Alberta Infant Motor Scale/AIMS), perfil psicológico materno (através da Escala de Depressão Pós-natal de Edimburgo/EPDS e Escala de Ansiedade de Hamilton), variáveis ambientais (medidas pelo Affordance in the home environment for development scale/AHEMD), cuidados maternos (avaliado através do Coding Interacting Behavior/CIB), bem como a coleta de leite (medição de ácidos graxos totais, proteínas e cortisol) e sangue materno (medição de hormônios séricos e interleucinas). Resultados: 51 crianças foram testadas em tarefas de conduta visual e outras medidas. As mães das crianças com baixos escores de fixação visual apresentaram maiores níveis de proteína no leite materno aos 3 meses. Quanto ao perfil metabólico materno, as mães das crianças que apresentaram melhores escores de fixação visual apresentaram melhores níveis séricos de T4 (no primeiro mês) e prolactina (no terceiro mês). Conclusão: O desenvolvimento neuromotor precoce do bebê, especialmente as habilidades visuais e de motricidade fina, estão intimamente associados aos fatores biológicos maternos (fatores metabólicos maternos e composição do leite materno). / Objective: To describe biological and environmental characteristics associated with fine motor skills measured by different levels of visual tracking in infants of 1 and 3 months. Study design: 82 mother-infant dyads were recruited during prenatal consultations or immediately after birth and visited at two times for data collection (25-40 and 85-100 days after birth). During the visits were collected maternal factors (maternal age, education level, type of delivery, number of antenatal consultations, type of breastfeeding and smoking), biological characteristics of the baby (gender, gestational age, birth, weight, head circumference, Apgar), infant motor tests (through the Child Visuomotor Behavior Rating Scales and Alberta Infant Motor Scale/AIMS), maternal psychological profile (through the Edinburgh Postnatal Depression Scale/EPDS and Hamilton Anxiety Scale), environmental variables (measured by the Affordance in the home environment for development scale/AHEMD), maternal care (evaluated through Coding Interacting Behavior/CIB), as well as milk collection (measurement of total fatty acids, proteins and cortisol) and maternal blood (measurement of serum hormones and interleukins). Results: 51 children were tested on visual tracking tasks and other measures. The mothers of children with low visual fixation scores presented higher levels of protein in breastmilk at 3 months. Regarding the maternal metabolic profile, the mothers of the children who presented better visual conduct scores had better serum levels of T4 (in the first month) and prolactin (in the third month). Conclusion: Early neuromotor development of the baby, especially the visual and fine motor skills, are closely associated with maternal biological characteristics (metabolic factors and composition of breast milk).

No sistema cardiovascular, os hormônios da tireoide exercem uma importante ação, influenciando a captação de cálcio, o inotropismo e o cronotropismo cardíaco e a resistência vascular periférica. No entanto, uma exacerbação destas ações, causada pelo aumento da secreção dos hormônios da tireoide, gera uma quebra desta homeostase e o desenvolvimento de hipertireoidismo. O hipertireoidismo leva ao aumento do consumo de oxigênio, gerando uma situação de estresse oxidativo. A exposição crônica ao estresse oxidativo leva à ativação de fatores de transcrição e citocinas, causando hipertrofia de cardiomiócitos e progressão para insuficiência cardíaca com inflamação e apoptose. Logo, o objetivo deste trabalho foi avaliar o papel dos hormônios da tireoide sobre a ativação de vias inflamatórias e apoptóticas mediada pelo estresse oxidativo. Neste estudo, nós avaliamos parâmetros de estresse oxidativo e algumas citocinas envolvidas com as vias de sinalização inflamatória e apoptótica. Para isso, utilizamos 60 ratos wistar, divididos em 2 grupos: Controle e Tratado (T4), com um n de 30 animais por grupo. O grupo T4 foi submetido à indução de hipertireoidismo através da adição de L-tiroxina (T4 – 12mg/L) na água de beber por 28 dias. O grupo controle não recebeu tratamento com L-tiroxina. Houve desenvolvimento de hipertireoidismo e indução de hipertrofia cardíaca no grupo T4. Verificamos também o aumento de H2O2 no coração e redução de -SH em eritrócitos no grupo T4. Houve aumento de LDH no grupo T4, indicando dano tecidual. Por fim, houve redução de PGC1-α, além de uma redução do p53 e de Bcl2 e aumento da razão Bax/Bcl2 no grupo T4. Os resultados apontam para a ocorrência de estresse oxidativo, o que com potencial dano induziu uma redução de PGC1-α e de p53, que podem estar relacionados à ativação de proteínas apoptóticas, como observado pelo aumento da razão Bax/Bcl2 no grupo tratado. / In the cardiovascular system, the thyroid hormones play an important action, influencing the uptake of calcium, the cardiac inotropy and chronotropy and peripheral vascular resistance. However, an exacerbation of these actions, caused by increased secretion of thyroid hormones, generates a breach of this homeostasis and could lead to development of hyperthyroidism. Hyperthyroidism leads to increased oxygen consumption, generating oxidative stress. Chronic exposure to oxidative stress leads to the activation of transcription factors and cytokines, causing cardiomyocyte hypertrophy and progression to heart failure with inflammation and apoptosis. Therefore, the aim of this study was to evaluate the role of thyroid hormones on the activation of inflammatory pathways and apoptotic mediated by oxidative stress. In this study, we evaluated some oxidative stress parameters and cytokines involved in inflammatory and apoptosis signaling pathways. For this, we used 60 Wistar rats, divided into 2 groups: control and treated (T4), with an n of 30 animals per group. The group T4 was subjected to hyperthyroidism induction by the addition of L-thyroxine (T4 - 12mg / L) in their drinking water for 28 days. The control group received no treatment with L-thyroxine. There was development of hyperthyroidism and induction of cardiac hypertrophy in the T4 group. We noticed the increase of H2O2 in the heart and reduced -SH in erythrocytes in the T4 group. There was LDH increase in the T4 group, indicating tissue damage. Finally, a reduction of PGC1-α, as well as a reduction of p53 and Bax/Bcl2 ratio increase in the T4 group. The results point to the occurrence of oxidative stress, which with potential damage induced a PGC1-α and p53 reduction, wich can be related to the activation of apoptotic proteins, as observed by increased Bax / Bcl2 ratio in the treated group.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / As disfunções tireoidianas estão associadas com alterações no peso corporal, no entanto, não está estabelecido na literatura se pequenas alterações na função tireoidiana dentro dos valores de referência das concentrações séricas de tireotrofina (TSH) poderiam afetar o índice de massa corporal (IMC). A associação entre as concentrações séricas de TSH e o IMC em indivíduos eutireóideos tem sido foco de recentes e conflitantes estudos e uma possível explicação para os achados conflitantes é a existência de subgrupos da população onde essa associação se expressa de forma diferente. O objetivo desse trabalho foi investigar a associação entre o IMC e as concentrações séricas de TSH em mulheres com função tireoidiana normal e avaliar possível modificação de efeito da associação entre IMC e as concentrações séricas de TSH pelo tabagismo, menopausa e raça. Os dados foram obtidos em um estudo de base populacional realizado na cidade do Rio de Janeiro, Brasil, entre junho de 2004 e abril de 2005, com amostragem probabilística por conglomerado em três estágios. No primeiro estágio foram selecionados 100 setores censitários, no segundo 15 domicílios de cada setor e no terceiro uma mulher por domicílio. Das 1500 mulheres com 35 anos ou mais selecionadas, 1298 participaram do estudo, dentre estas, 1084 apresentavam função tireoidiana normal. Uma associação positiva e estatisticamente significante foi observada entre o IMC e o TSH sérico (β=0,90; p-valor=0,02) na população como um todo. A análise exploratória de subgrupos com diferentes graus de associação foi obtida pela análise de interações estatísticas. Os subgrupos de mulheres na pré-menopausa (β=1,04; p-valor=0,04), de raça negra (β=1,39; p-valor=0,14) e fumantes (β=1,78; p-valor=0,04), apresentaram associações de maior magnitude. Em conclusão, o TSH parece ter um papel modulador das mudanças no peso corporal, mesmo em mulheres com função tireoidiana normal. O tabagismo e a raça são fortes modificadores de efeito da associação entre TSH e IMC e futuros estudos devem considerar estes fatores. / Although, overt thyroid dysfunction is associated with weight changes, it is not known whether minor changes in thyroid function within normal serum thyrotropin (TSH) concentration could affect body mass index (BMI). The association between serum TSH and BMI in euthyroid subjects has been focus of recent and controversial studies. A possible explanation for these controversial findings could be the differences on this association between population subgroups. The aim of this study was to investigate the association between BMI and TSH in women with normal thyroid function and to evaluate a potential effect modification on the association between BMI and TSH by smoking, race, and menopause status. A population-based study was carried out in the city of Rio de Janeiro, Brazil, in 2004-2005. Sample selection was based on a three-stage cluster design. In the first stage, 100 primary sample units (PSU) were selected. In the second stage, 15 households were select from each PSU and in the third stage one woman was selected from each household. Of a sample of 1500 women aged 35 years or older, 1298 agree to participate. For the present study, a final sample of 1084 women without thyroid disease was investigated. Overall, BMI was positively and significantly associated with serum TSH (β=0.90; p- value=0.02) and stronger association between BMI and serum TSH among premenopausal women (β=1.04; p-value=0.04), Black women (β=1.39; p-value=0.14) and smokers (β=1.77; p-value=0.04) was found. In conclusion, TSH appears to modulate body weight among women even in the normal range. Smoking and race are strong effect modifiers of the association between TSH and BMI and future studies should take these effect modifiers into account.

Le cerveau adulte des mammifères conserve sa capacité à générer de nouvelles cellules cérébrales à partir de cellules souches neurales (CSNs), principalement localisées dans deux régions cérébrales spécifiques, l'hippocampe et la zone sous-ventriculaire (SVZ). Ce processus, appelé neurogenèse, permet la formation de nouveaux neurones et de nouvelles cellules gliales (astrocytes et oligodendrocytes). Différents signaux contrôlent la prolifération et la différenciation des CSNs. Parmi ces signaux, les hormones thyroïdiennes (HTs) sont impliquées dans la prolifération des CSNs de la SVZ et dans la différenciation neuronale. À l’inverse des cellules différenciées, telles que les neurones ou les glies, les CSNs ont un fonctionnement – ou métabolisme – principalement basé sur la glycolyse et sur une faible respiration mitochondriale. Or l'évolution du métabolisme des CSNs peut influencer leur choix de destin cellulaire. Les HTs jouant un rôle important dans l'activation du métabolisme mitochondrial, j'ai testé l'hypothèse selon laquelle le choix du destin des CSNs de la SVZ adulte se ferait grâce à l'influence de la signalisation thyroïdienne sur l'activité mitochondriale. J'ai tout d'abord montré in vivo et in vitro que les HTs permettent la détermination des CSNs en précurseurs neuronaux dans la SVZ, tandis qu'une période d'hypothyroïdisme favorise la détermination gliale. La transthyrétine, protéine de liaison des HTs, est spécifiquement présente dans les cellules de la SVZ ayant un destin neuronal, alors que la désiodase de type 3, inactivatrice des HTs, est exprimée par les précurseurs oligodendrocytaires (OPCs), indiquant une activationdifférentielle de la signalisation thyroïdienne dans les deux lignages cellulaires. Par ailleurs j'ai pu observer que les cellules s'engageant vers un destin neuronal possèdent une plus grande activité mitochondriale que les OPCs. La présence d'HTs favorise de plus la respiration mitochondriale, ainsi que la production de dérivés réactifs de l'oxygène (ROS) issus de l'activité des mitochondries, dans les cellules de la SVZ. Un blocage des protéines de la chaîne respiratoire empêche les HTs de promouvoir la détermination neuronale, montrant la nécessité de l'activation mitochondriale pour l'engagement des CSNs en précurseurs neuronaux. On sait d'autre part que les modifications morphologiques (ou dynamiques) mitochondriales sont nécessaires à l'augmentation de la respiration. La division (ou fission) des mitochondries est en particulier essentielle à une bonne répartition intracellulaire de la production de l'énergie issue de la respiration, ainsi qu'à la migration cellulaire. Dans les cellules de la SVZ, j'ai montré que l'action des HTs permet l'activation de la protéine DRP1, médiatrice de la fission mitochondriale, et ce principalement dans les cellules du lignage neuronal. Les HTs favorisent donc la détermination des CSNs de la SVZ vers un destin neuronal grâce à l'activation de la respiration et de la fission mitochondriales. / The adult mammalian brain maintains its capacity to generate new cells from neural stem cells (NSCs), mainly localized in two specific brain regions, the hippocampus and the sub-ventricular zone (SVZ). This process, named neurogenesis, results in the production of new neurons and new glial cells (astrocytes and oligodendrocytes). Several signals control NSCs proliferation and differentiation. Among those, thyroid hormones (THs) are involved in NSCs proliferation in the SVZ and in neuronal differentiation. NSC metabolism relies mainly on glycolysis associated with a low mitochondrial activity, whereas mature cells, like neurons and glia, preferentially use oxidative phosphorylation. Changes in NSC metabolism can impact cell fate. As THs play an important part in activating mitochondrial metabolism, I hypothesized that the influence of TH signaling on mitochondrial activity triggers NSC fate choice in the adult SVZ. First, I showed in vivo and in vitro that THs allow NSC determination in neuronal precursors, whereas a short hypothyroidism favors glial determination. Transthyretine, a TH binding protein, is specifically present in the SVZ cells having a neuronal fate, while type 3 deiodinase, a TH inhibitor, is expressed by oligodendrocyte precursor cells (OPCs). These results indicate that THs signaling isdifferentially activated in neuronal and glial cell lineages. I observed that cells adopting a neuronal fate display a greater mitochondrial activity when compared to OPCs, and that TH signaling favors mitochondrial respiration and ROS production in the SVZ cells. Inhibiting the mitochondrial respiratory chain prevents TH-mediated promotion of neuronal determination, proving the need of mitochondrial activation for NSC commitment toward a neuronal phenotype. Besides, it is also known that modifications of mitochondrial morphology (or mitochondrial dynamics) are required for the respiration to increase. Among mitochondrial dynamics, fission is crucial for a good intracellular repartition of energy production, and for cell migration. In the SVZ cells, I showed that, DRP1, the main inducer of mitochondrial fission, is activated by THs mainly in cells adopting a neuronal fate. Thus, THs favor NSC fate choice toward a neuronal phenotype through the activation of mitochondrial metabolism and mitochondrial fission in the adult mouse SVZ.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / As disfunções tireoidianas estão associadas com alterações no peso corporal, no entanto, não está estabelecido na literatura se pequenas alterações na função tireoidiana dentro dos valores de referência das concentrações séricas de tireotrofina (TSH) poderiam afetar o índice de massa corporal (IMC). A associação entre as concentrações séricas de TSH e o IMC em indivíduos eutireóideos tem sido foco de recentes e conflitantes estudos e uma possível explicação para os achados conflitantes é a existência de subgrupos da população onde essa associação se expressa de forma diferente. O objetivo desse trabalho foi investigar a associação entre o IMC e as concentrações séricas de TSH em mulheres com função tireoidiana normal e avaliar possível modificação de efeito da associação entre IMC e as concentrações séricas de TSH pelo tabagismo, menopausa e raça. Os dados foram obtidos em um estudo de base populacional realizado na cidade do Rio de Janeiro, Brasil, entre junho de 2004 e abril de 2005, com amostragem probabilística por conglomerado em três estágios. No primeiro estágio foram selecionados 100 setores censitários, no segundo 15 domicílios de cada setor e no terceiro uma mulher por domicílio. Das 1500 mulheres com 35 anos ou mais selecionadas, 1298 participaram do estudo, dentre estas, 1084 apresentavam função tireoidiana normal. Uma associação positiva e estatisticamente significante foi observada entre o IMC e o TSH sérico (β=0,90; p-valor=0,02) na população como um todo. A análise exploratória de subgrupos com diferentes graus de associação foi obtida pela análise de interações estatísticas. Os subgrupos de mulheres na pré-menopausa (β=1,04; p-valor=0,04), de raça negra (β=1,39; p-valor=0,14) e fumantes (β=1,78; p-valor=0,04), apresentaram associações de maior magnitude. Em conclusão, o TSH parece ter um papel modulador das mudanças no peso corporal, mesmo em mulheres com função tireoidiana normal. O tabagismo e a raça são fortes modificadores de efeito da associação entre TSH e IMC e futuros estudos devem considerar estes fatores. / Although, overt thyroid dysfunction is associated with weight changes, it is not known whether minor changes in thyroid function within normal serum thyrotropin (TSH) concentration could affect body mass index (BMI). The association between serum TSH and BMI in euthyroid subjects has been focus of recent and controversial studies. A possible explanation for these controversial findings could be the differences on this association between population subgroups. The aim of this study was to investigate the association between BMI and TSH in women with normal thyroid function and to evaluate a potential effect modification on the association between BMI and TSH by smoking, race, and menopause status. A population-based study was carried out in the city of Rio de Janeiro, Brazil, in 2004-2005. Sample selection was based on a three-stage cluster design. In the first stage, 100 primary sample units (PSU) were selected. In the second stage, 15 households were select from each PSU and in the third stage one woman was selected from each household. Of a sample of 1500 women aged 35 years or older, 1298 agree to participate. For the present study, a final sample of 1084 women without thyroid disease was investigated. Overall, BMI was positively and significantly associated with serum TSH (β=0.90; p- value=0.02) and stronger association between BMI and serum TSH among premenopausal women (β=1.04; p-value=0.04), Black women (β=1.39; p-value=0.14) and smokers (β=1.77; p-value=0.04) was found. In conclusion, TSH appears to modulate body weight among women even in the normal range. Smoking and race are strong effect modifiers of the association between TSH and BMI and future studies should take these effect modifiers into account.