Genomic imprinting of the type 3 thyroid hormone deiodinase gene: Regulation and developmental implications

Charalambous, Marika; Hernández, Arturo

doi:10.1016/j.bbagen.2012.03.015

Cited by 31 publications

(18 citation statements)

References 134 publications

(144 reference statements)

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“…Both deiodinases are known targets of epigenetic regulation. During muscle cell differentiation, dio2 gene expression is up-regulated by histone demethylation and acetylation leading to myoblast differentiation (32), whereas dio3 sits in an imprinted locus, tightly regulated by epigenetic mechanisms essential for normal growth and viability (33). In addition, it has been reported that photoperiodic information regulates dio3 gene expression by acting upon promoter methylation in adult Siberian hamsters (34).…”

Section: Discussionmentioning

confidence: 99%

Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

Miera

Bothorel

Jaeger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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In wild mammals, offspring development must anticipate forthcoming metabolic demands and opportunities. Within species, different developmental strategies may be used, dependent on when in the year conception takes place. This phenotypic flexibility is initiated before birth and is linked to the pattern of day length (photoperiod) exposure experienced by the mother during pregnancy. This programming depends on transplacental communication via the pineal hormone melatonin. Here, we show that, in the Siberian hamster (Phodopus sungorus), the programming effect of melatonin is mediated by the pars tuberalis (PT) of the fetal pituitary gland, before the fetal circadian system and autonomous melatonin production is established. Maternal melatonin acts on the fetal PT to control expression of thyroid hormone deiodinases in ependymal cells (tanycytes) of the fetal hypothalamus, and hence neuroendocrine output. This mechanism sets the trajectory of reproductive and metabolic development in pups and has a persistent effect on their subsequent sensitivity to the photoperiod. This programming effect depends on tanycyte sensitivity to thyroid stimulating hormone (TSH), which is dramatically and persistently increased by short photoperiod exposure in utero. Our results define the role of the fetal PT in developmental programming of brain function by maternal melatonin and establish TSH signal transduction as a key substrate for the encoding of internal calendar time from birth to puberty.photoperiodism | developmental programming | hypothalamus | pars tuberalis | thyroid

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Section: Discussionmentioning

confidence: 99%

Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

Miera

Bothorel

Jaeger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The Dio3 gene that encodes D3 has been shown to be imprinted in the mouse and is preferentially expressed by the paternal allele (Hernandez et al 2002, Tsai et al 2002. However, imprinting does not occur in all fetal tissues and, where it does, expression from the paternal allele varies from 75-85% in fetal tissues to 50-60% of total expression in the placenta (Charalambous & Hernandez 2013). Knockout of the Dio3 gene causes perinatal thyrotoxicity and partial lethality at or before birth (Hernandez et al 2006).…”

Section: Metabolism Of Thyroid Hormones In Uteromentioning

confidence: 99%

Thyroid hormones in fetal growth and prepartum maturation

Forhead

Fowden

2014

Journal of Endocrinology

341

270

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The thyroid hormones, thyroxine (T 4 ) and triiodothyronine (T 3 ), are essential for normal growth and development of the fetus. Their bioavailability in utero depends on development of the fetal hypothalamic-pituitary-thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T 4 and T 3 concentrations are also affected by gestational age, nutritional and endocrine conditions in utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating the prepartum maturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T 4 and T 3 bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

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“…The DIO3 gene is imprinted, with preferential expression of the paternal allele. It belongs to a cluster of imprinted regions, at the DLK1-DIO3 locus (11). …”

Section: Type 3 Deiodinase and Inactivation Of Thyroid Hormonesmentioning

confidence: 99%

Type 3 Deiodinase and Consumptive Hypothyroidism: A Common Mechanism for a Rare Disease

Luongo¹,

Trivisano²,

Alfano³

et al. 2013

Front. Endocrinol.

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The major product secreted by the thyroid is thyroxine (T4), whereas most of the biologically active triiodothyronine (T3) derives from the peripheral conversion of T4 into T3. The deiodinase enzymes are involved in activation and inactivation of thyroid hormones (THs). Type 1 and type 2 deiodinase (D1 and D2) convert T4 into T3 whereas D3 degrades T4 and T3 into inactive metabolites and is thus the major physiological TH inactivator. The hypothalamic-pituitary-thyroid axis maintains circulating TH levels constant, while the deiodinases tissue-specifically regulate intracellular thyroid status by controlling TH action in a precise spatio-temporal fashion. Here we review the data related to the recent identification of a paraneoplastic syndrome called “consumptive hypothyroidism,” which exemplifies how deiodinases alter substantially the concentration of TH in blood. This syndrome results from the aberrant uncontrolled expression of D3 that can induce a severe form of hypothyroidism by inactivating T4 and T3 in defined tumor tissue. This rare TH insufficiency generally affects patients in the first years of life, and has distinct features in terms of diagnosis, treatment, and prognosis with respect to other forms of hypothyroidism.

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Genomic imprinting of the type 3 thyroid hormone deiodinase gene: Regulation and developmental implications

Cited by 31 publications

References 134 publications

Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

Maternal photoperiod programs hypothalamic thyroid status via the fetal pituitary gland

Thyroid hormones in fetal growth and prepartum maturation

Type 3 Deiodinase and Consumptive Hypothyroidism: A Common Mechanism for a Rare Disease

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