Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone.

Mitsuhashi, Tsutomu; Tennyson, G E; Nikodem, Vera M.

doi:10.1073/pnas.85.16.5804

Cited by 274 publications

(159 citation statements)

References 22 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…The Thrb gene encodes three T 3 -binding TRb isoforms (b1, b2 and b3) whereas the Thra gene encodes one T 3 -binding TRa1 and two splicing variants (TRa2 and TRa3). These TRa variants have no T 3 -binding activity (Mitsuhashi et al 1988). We found that both isoforms Thra1 and Thrb1 were expressed in rat HG; Thra1 mRNA levels were higher than Thrb1 levels, given the much lower normalised Ct values (Fig.…”

Section: Thra and Thrb Expressionmentioning

confidence: 82%

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Santillo

Burrone

Falvo

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor (Tra (Thra) and Trb (Thrb)) are expressed in rat HGs. Although Thra is expressed at a higher level, only Thrb is regulated by triiodothyronine (T 3 ). Because T 3 induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of T 3 to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T 3 modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by w50% in hypothyroid T 3 -treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1 and Tfam, whereas T 3 treatment increased the expression level of these genes.

show abstract

Section: Thra and Thrb Expressionmentioning

confidence: 82%

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Santillo

Burrone

Falvo

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…In contrast, TRa is moderately expressed in several tissues. The a1 to a2 ratio is variable, being the most contrasted in the brain (Mitsuhashi et al, 1988). It has been suggested that the particular organization of the TRa locus contributes to the regulation of the a1/a2 balance.…”

Section: Introductionmentioning

confidence: 99%

Activation of the thyroid hormone receptor α gene promoter by the orphan nuclear receptor ERRα

et al. 1998

View full text Add to dashboard Cite

The superfamily of nuclear receptors comprises transcription factors that depend on a ligand for their activity. In addition, the superfamily includes a number of orphan receptors, for which no ligand is known. We report here that the orphan receptor estrogen receptor related alpha receptor (ERRa) stimulates the expression of the thyroid hormone receptor alpha (TRa) gene promoter. We characterized a responsive site that is both necessary and su cient for ERRa-induced transactivation. In addition, we show that both TRa and ERRa are coexpressed in embryonic intestine, brown fat and heart as well as in the adult gonads. In the testis, expression of both receptors can be found in the seminiferous tubes where it is totally restricted to spermatocytes I. Altogether this suggests that TRa is an in vivo target of ERRa.

show abstract

“…In addition to the three transcripts (TR␣1, TR␤1, TR␤2) encoding isoforms that bind T3, we examined two closely related TR␣ splice variants collectively designated TR␣2. These variants give rise to isoforms that do not bind T3, but they are expressed at high levels in the developing brain (Lazar et al, 1988;Mitsuhashi et al, 1988a;Strait et al, 1990). As illustrated in Figure 6 A, TR␣1 mRNA and TR␤1 mRNA, but not TR␤2 or TR␣2 transcripts, were detected in microglia kept in vitro for up to 24 hr after purification from primary glial cultures.…”

Section: Expression Of Tr By Cultured Microglial Cellsmentioning

confidence: 99%

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

et al. 2001

View full text Add to dashboard Cite

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3Ј-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life.Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the ␣1 and ␤1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

show abstract

Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone.

Abstract: The nucleotide and predicted amino acid sequences of two variant cDNAs [rat brain thyroid hormone receptor (rTRa) vI and vI], isolated from a rat brain cDNA library by using the Pst I fragment of v-erbA, showed virtual identity with the rat brain thyroid hormone receptor (rTRa)

Cited by 274 publications

References 22 publications

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland

Activation of the thyroid hormone receptor α gene promoter by the orphan nuclear receptor ERRα

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

Contact Info

Product

Resources

About