A Complex Deoxyribonucleic Acid Response Element in the Rat Ca2+/Calmodulin-Dependent Protein Kinase IV Gene 5′-Flanking Region Mediates Thyroid Hormone Induction and Chicken Ovalbumin Upstream Promoter Transcription Factor 1 Repression

Liu, Yanyun; Brent, Gregory A.

doi:10.1210/me.2001-0324

Cited by 25 publications

(23 citation statements)

References 71 publications

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“…Based on these data, we propose that Camk4 regulation is an essential part of an amplifying mechanism for T 3 action in the fetal brain at stages where both the concentration of T 3 and that of receptor are still low. In support of this proposal, a thyroid hormone-responsive element has been identified in the Camk4 gene promoter (39), and as we show here, the stimulation by T 3 in cultured neurons was direct.…”

Section: Significance Of Camk4 Inductionsupporting

confidence: 85%

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Thyroid Hormone Regulation of Gene Expression in the Developing Rat Fetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway

Morte

Díez

Ausó³

et al. 2010

Endocrinology

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Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the second trimester, a period of high sensitivity of the brain to thyroid hormones. In the rat, the equivalent period is the last quarter of pregnancy. However, little is known about thyroid hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated genes have been identified during the postnatal period. To identify potential targets of thyroid hormone in the fetal brain, we induced maternal and fetal hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto-1-methylimidazole) treatment. Microarray analysis identified differentially expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after conception. Gene function analysis revealed genes involved in the biogenesis of the cytoskeleton, neuronal migration and growth, and branching of neurites. Twenty percent of the differentially expressed genes were related to each other centered on the Ca 2ϩ and calmodulin-activated kinase (Camk4) pathway. Camk4 was regulated directly by T 3 in primary cultured neurons from fetal cortex, and the Camk4 protein was also induced by thyroid hormone. No differentially expressed genes were recovered when euthyroid fetuses from hypothyroid mothers were compared with fetuses from normal mothers. Although the results do not rule out a specific contribution from the mother, especially at earlier stages of pregnancy, they indicate that the main regulators of thyroid hormone-dependent, fetal brain gene expression near term are the fetal thyroid hormones. (Endocrinology 151: 810-820, 2010)

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Section: Significance Of Camk4 Inductionsupporting

confidence: 85%

“…Camk4 was previously shown to be induced by T 3 in rat fetal telencephalic cultures (37,38) and in mouse embryonic stem cells (39). Developmental expression of Camk4 correlates with periods of neuronal differentiation and apoptosis (40) and has been implicated in brain-derived neurotrophic factor (BDNF) action (41).…”

Section: Significance Of Camk4 Inductionmentioning

confidence: 99%

Thyroid Hormone Regulation of Gene Expression in the Developing Rat Fetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway

Morte

Díez

Ausó³

et al. 2010

Endocrinology

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“…Thyroid hormone responsiveness of the brain is associated with reduced expression of COUP-TF1. Numerous thyroid hormone gene targets have been identified with overlapping TR and COUP-TF1 response elements (99,100). The expression of COUP-TF1 blocks TR from binding the TRE, consistent with protection from early T3 stimulation.…”

Section: Tr Isoforms and Neural Developmentmentioning

confidence: 86%

Mechanisms of thyroid hormone action

Brent¹

2012

J. Clin. Invest.

Self Cite

894

632

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Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform-specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function.

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“…In addition to control of Purkinje cell specific genes, COUP-TF1 also regulates control of Ca 2+ / calmodulin-dependent protein kinase IV (CaMKIV) expression in granule neurons (99). CaMKIV is abundantly expressed in the developing cerebellar granule cell (100,101).…”

Section: Th Deiodination and The Developing Cerebellummentioning

confidence: 99%

Thyroid hormone and cerebellar development

Anderson

2008

Cerebellum

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Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

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A Complex Deoxyribonucleic Acid Response Element in the Rat Ca2+/Calmodulin-Dependent Protein Kinase IV Gene 5′-Flanking Region Mediates Thyroid Hormone Induction and Chicken Ovalbumin Upstream Promoter Transcription Factor 1 Repression

Cited by 25 publications

References 71 publications

Thyroid Hormone Regulation of Gene Expression in the Developing Rat Fetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway

Thyroid Hormone Regulation of Gene Expression in the Developing Rat Fetal Cerebral Cortex: Prominent Role of the Ca2+/Calmodulin-Dependent Protein Kinase IV Pathway

Mechanisms of thyroid hormone action

Thyroid hormone and cerebellar development

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