Video Experimental Relacionado
Updated: Jul 10, 2026
10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
El receptor de la hormona tiroidea se une con efectos de transcripción opuestos a un motivo de secuencia común en los
C K Glass1, J M Holloway, O V Devary
1Eukaryotic Regulatory Biology Program, School of Medicine, University of California, San Diego, La Jolla 92093-0613.
Cell
|July 29, 1988
Resumen
Los receptores de la hormona tiroidea (T3) se unen a secuencias específicas de ADN, activando la transcripción. Sin embargo, se unen a los elementos de respuesta al estrógeno sin activación, inhibiendo el estrógeno.
Área de la Ciencia:
- Biología molecular La biología molecular.
- Endocrinología Endocrinología.
- Genética La genética.
Sus antecedentes:
- Los receptores de la hormona tiroidea (T3) regulan la expresión génica.
- Los elementos de respuesta al estrógeno (EREs) son secuencias de ADN unidas por receptores de estrógeno.
- Los requisitos precisos de unión al ADN para la activación transcripcional del receptor T3 no se comprenden completamente.
Objetivo del estudio:
- Para investigar la especificidad de unión al ADN del receptor T3.
- Para determinar las consecuencias funcionales de la unión del receptor T3 a los elementos de respuesta al estrógeno.
- Aclarar el mecanismo por el cual los receptores T3 interactúan con las EREs.
Principales métodos:
- Ensayos de desplazamiento de movilidad electroforética (EMSA) para evaluar la unión al ADN in vitro.
- En ensayos de activación transcripcional in vivo se utilizan sistemas de genes reporteros.
- Análisis de secuencias de ADN con variaciones en el motivo central palíndromo.
Principales resultados:
- El receptor T3 se une a secuencias de ADN con un motivo de núcleo palíndromo (5 omino-TCAGGTCA.TGACCTGA-3 omino) y una "brecha" central.
- El receptor T3 se une con alta afinidad a las EREs (que carecen de una brecha) in vitro.
- El receptor T3 no activa la transcripción de las EREs in vivo e inhibe la transactivación mediada por estrógeno.
Conclusiones:
- Solo un subconjunto de los elementos de unión al ADN de los receptores T3 funcionan como elementos de respuesta T3.
- La unión del receptor T3 a las EREs es transcripcionalmente inactiva y compite con la unión al receptor de estrógeno.
- Esta competencia conduce a una disminución neta en la expresión génica dependiente del estrógeno.
Videos de Conceptos Relacionados
01:08Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
01:31Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:22Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
01:20Synthesis and Regulation of Thyroid Hormones
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...