Spelling suggestions: "subject:"thyroid hormone receptors (TRs)"" "subject:"hyroid hormone receptors (TRs)""
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Efeito da reposição do hormônio do crescimento (GH) no desenvolvimento ósseo de ratas hipotireoideas tratadas com o agonista seletivo do receptor <font face=\"symbol\">b de hormônio tireoideano GC-1. / Effect of growth hormone (GH) replacement on bone development of hypothyroid rats treated with the thyroid hormone receptor <font face=\"symbol\">b-selective agonist GC-1.Freitas, Fatima Rodrigues de Sousa e 28 May 2008 (has links)
Sabe-se que o hipotireoidismo (Hipo) resulta em supressão do eixo hormônio de crescimento (GH)/ insulin-like growth factor I (IGF-I) e em atraso no desenvolvimento esquelético. Em um estudo anterior, vimos que o tratamento de ratas jovens Hipo com GC-1, um análogo da triiodotironina (T3) seletivo pela isoforma <font face=\"symbol\">b de receptor de hormônio tireoideano (TR<font face=\"symbol\">b), não teve efeito sobre o IGF-I sérico ou sobre a expressão protéica de IGF-I nas lâminas epifisiais, mas parcialmente reverteu alterações esqueléticas decorrentes do Hipo, o que sugere que: (i) o desenvolvimento esquelético requer ações do T3 mediadas pelo TR<font face=\"symbol\">a1 e TR<font face=\"symbol\">b1 (isoformas de TR expressas no osso); ou (ii) requer interações entre o eixo GH/IGF-I e o hormônio tireoideano. Neste estudo, investigamos essas hipóteses tratando ratas recém desmamadas Hipo com T3 ou GC-1 em associação ou não com o GH por 4 semanas. Os nossos achados mostram que o T3 e GH interagem para promover o desenvolvimento ósseo, mas que uma série de efeitos do T3 nesse processo independe do eixo GH/IGF-I e são mediadas pelo TR<font face=\"symbol\">a e/ou TR<font face=\"symbol\">b. / Thyroid hormone (TH) has important effects on bone development and metabolism. It is known that triiodotyronine (T3) has indirect actions in the skeleton through its influence on the production and secretion of growth hormone (GH)/ insulin-like growth factor (IGF-I) and/or other factors. On the other hand, direct actions of T3 on bone are recognized but not yet clear. Most of T3 action is mediaded by its nuclear receptors (TRs). TR<font face=\"symbol\">a1, TR<font face=\"symbol\">b1 e TR<font face=\"symbol\">b2 bind T3, while TR<font face=\"symbol\">a2 does not bind T3 and acts as an antagonist of genic transcription of TR<font face=\"symbol\">a1 and TR<font face=\"symbol\">b1. All these receptors, except TR<font face=\"symbol\">b2, are expressed in chondrocytes of growth plate, osteoblasts and osteoclastos. However, the functional roles of each TR isoformas in the bone development are incompletely understood. A few years, it is development GC-1, a synthetic analog of T3 which is selectivwe for TR<font face=\"symbol\">b1 over TR<font face=\"symbol\">a1. In recent study, we showed that treatment of hypothyroid young rats with T3 revert the IGF-I deficiency and skeleton defects caused by hypothyroidism. Since GC-1 treatment does not effects on serum levels of IGF-I or protein expression of IGF-I in the growth plate, but revert some bone alterations induced by T3 deficiency. Considering the selectivity of GC-1 for TR<font face=\"symbol\">b, these findings suggest that T3 has effects on bone development that are mediated by TR<font face=\"symbol\">b and independent of GH/IGF-I axis. On the other hand, the inability of GC-1 in completely revert the alterations of bone development suggests that the normal skeleton development require (i) T3 actions mediated by TR<font face=\"symbol\">a1 and TR<font face=\"symbol\">b1, or (ii) synergic or additive actions between GH/IGF-I axis and thyroid hormone. To investigate these hypotheses, 21 day-old hypothyroid female rats were treated with T3 or GC-1 in association or not with GH for 4 weeks. Our findings show that T3 interacts with GH to promote body growth, differentiation of growth plate hypertrofic chondrocytes, intramembranous ossification of cranial bone, and increased of bone resistance and other biomechanics parameters that contribute to the best bone quality. On the other hand, ours results suggest strongly that TH acts in bone mass acquisition, in organization of growth plate chondrocytes and endocondral ossification mainly independent of GH/IGF-I axis and via TR<font face=\"symbol\">a and/or TR<font face=\"symbol\">b.
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Efeito da reposição do hormônio do crescimento (GH) no desenvolvimento ósseo de ratas hipotireoideas tratadas com o agonista seletivo do receptor <font face=\"symbol\">b de hormônio tireoideano GC-1. / Effect of growth hormone (GH) replacement on bone development of hypothyroid rats treated with the thyroid hormone receptor <font face=\"symbol\">b-selective agonist GC-1.Fatima Rodrigues de Sousa e Freitas 28 May 2008 (has links)
Sabe-se que o hipotireoidismo (Hipo) resulta em supressão do eixo hormônio de crescimento (GH)/ insulin-like growth factor I (IGF-I) e em atraso no desenvolvimento esquelético. Em um estudo anterior, vimos que o tratamento de ratas jovens Hipo com GC-1, um análogo da triiodotironina (T3) seletivo pela isoforma <font face=\"symbol\">b de receptor de hormônio tireoideano (TR<font face=\"symbol\">b), não teve efeito sobre o IGF-I sérico ou sobre a expressão protéica de IGF-I nas lâminas epifisiais, mas parcialmente reverteu alterações esqueléticas decorrentes do Hipo, o que sugere que: (i) o desenvolvimento esquelético requer ações do T3 mediadas pelo TR<font face=\"symbol\">a1 e TR<font face=\"symbol\">b1 (isoformas de TR expressas no osso); ou (ii) requer interações entre o eixo GH/IGF-I e o hormônio tireoideano. Neste estudo, investigamos essas hipóteses tratando ratas recém desmamadas Hipo com T3 ou GC-1 em associação ou não com o GH por 4 semanas. Os nossos achados mostram que o T3 e GH interagem para promover o desenvolvimento ósseo, mas que uma série de efeitos do T3 nesse processo independe do eixo GH/IGF-I e são mediadas pelo TR<font face=\"symbol\">a e/ou TR<font face=\"symbol\">b. / Thyroid hormone (TH) has important effects on bone development and metabolism. It is known that triiodotyronine (T3) has indirect actions in the skeleton through its influence on the production and secretion of growth hormone (GH)/ insulin-like growth factor (IGF-I) and/or other factors. On the other hand, direct actions of T3 on bone are recognized but not yet clear. Most of T3 action is mediaded by its nuclear receptors (TRs). TR<font face=\"symbol\">a1, TR<font face=\"symbol\">b1 e TR<font face=\"symbol\">b2 bind T3, while TR<font face=\"symbol\">a2 does not bind T3 and acts as an antagonist of genic transcription of TR<font face=\"symbol\">a1 and TR<font face=\"symbol\">b1. All these receptors, except TR<font face=\"symbol\">b2, are expressed in chondrocytes of growth plate, osteoblasts and osteoclastos. However, the functional roles of each TR isoformas in the bone development are incompletely understood. A few years, it is development GC-1, a synthetic analog of T3 which is selectivwe for TR<font face=\"symbol\">b1 over TR<font face=\"symbol\">a1. In recent study, we showed that treatment of hypothyroid young rats with T3 revert the IGF-I deficiency and skeleton defects caused by hypothyroidism. Since GC-1 treatment does not effects on serum levels of IGF-I or protein expression of IGF-I in the growth plate, but revert some bone alterations induced by T3 deficiency. Considering the selectivity of GC-1 for TR<font face=\"symbol\">b, these findings suggest that T3 has effects on bone development that are mediated by TR<font face=\"symbol\">b and independent of GH/IGF-I axis. On the other hand, the inability of GC-1 in completely revert the alterations of bone development suggests that the normal skeleton development require (i) T3 actions mediated by TR<font face=\"symbol\">a1 and TR<font face=\"symbol\">b1, or (ii) synergic or additive actions between GH/IGF-I axis and thyroid hormone. To investigate these hypotheses, 21 day-old hypothyroid female rats were treated with T3 or GC-1 in association or not with GH for 4 weeks. Our findings show that T3 interacts with GH to promote body growth, differentiation of growth plate hypertrofic chondrocytes, intramembranous ossification of cranial bone, and increased of bone resistance and other biomechanics parameters that contribute to the best bone quality. On the other hand, ours results suggest strongly that TH acts in bone mass acquisition, in organization of growth plate chondrocytes and endocondral ossification mainly independent of GH/IGF-I axis and via TR<font face=\"symbol\">a and/or TR<font face=\"symbol\">b.
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Regulace genové exprese jadernými receptory ve specifickém metabolickém kontextu - evoluční perspektiva / Gene expression regulation by nuclear receptors in a specific metabolic context - evolutionary perspectiveKaššák, Filip January 2021 (has links)
In animals, some of the most critical regulators of gene expression are nuclear hormone receptors (NRs) and their coregulators, specifically the Mediator complex. Of particular interest are the NRs implicated in metabolic and developmental regulation and in carcinogenesis: thyroid hormone receptors (TRs) and retinoid X receptors (RXRs). In this work, I venture to elucidate some aspects of gene expression regulation by these NRs: the degree of evolutionary conservation of signalling based on NRs and their coregulators; the mechanisms of negative regulation by NRs; and possible implications of these findings for clinical medicine. State-of-the-art bioinformatical, genome editing and microscopic techniques are applied at three levels of animal evolution to study NRs and Mediator. Reverse genomics in human patients suffering from the syndrome of resistance to thyroid hormones β are used to infer the structure and function of TRβ subdomains. Alignments, binding studies and in vivo experiments in Trichoplax adhaerens allow identification of a close orthologue of human RXR at the basis of metazoan evolution. Employing database queries, genome editing and microscopy, we describe a correct orthologue of the Mediator subunit 28 in Caenorhabditis elegans, indicating a complete homology of the Mediator complex...
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