The expression of thyroid hormone receptors (THR) is regulated by the progesterone receptor system in first trimester placental tissue and in BeWo cells in vitro

Abstract The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the half-site of the estrogen-response element (ERE) and a consensus sequence constituting the thyroid hormone-response element. Because of the potential for thyroid hormone (T3) to affect estrogen (E)- and progesterone-dependent female reproductive behavior via EREs, we have begun to investigate the activity of an ERE identified in the progesterone receptor (PR) proximal promoter and its interactions with the estrogen receptor (ER) and thyroid hormone receptors (TR). In addition, we have compared ER and TR interactions on the PR ERE construct with that of the vitellogenin A2 (vit A2) consensus ERE. Electrophoretic mobility shift assays demonstrated that TR binds to the PR ERE as well as to the consensus ERE sequence in vitro. Further, these two EREs were differentially regulated by T3 in the presence of TR. T3 in the presence of TRα increased transcription from a PR ERE construct ∼5-fold and had no inhibitory effect on E induction. Similarly, T3 also activated a β-galactosidase reporter construct containing PR promoter sequences spanning −1400 to +700. In addition, the TR isoforms β1 and β2 also stimulated transcription from the PR ERE construct by 5- to 6-fold. A TRα mutant lacking the ability to bind AGGTCA sequences in vitro failed to activate transcription from the PR ERE construct, demonstrating dependence on DNA binding. In contrast to its actions on the PR ERE construct, TRα did not activate transcription from the vit A2 consensus ERE but rather attenuated E-mediated transcriptional activation. Attenuation from the vit A2 consensus ERE is not necessarily dependent on DNA binding as the TRα DNA binding mutant was still able to inhibit E-dependent transactivation. In contrast to TRα, the isoforms TRβ1 and TRβ2 failed to inhibit E-induced activation from the vit A2 consensus ERE. These results demonstrate that the PR ERE construct differs from the vit A2 consensus ERE in its ability to respond to TRs and that divergent pathways exist for activation and inhibition by TR. Since ERs, PRs, and TRs are all present in hypothalamic neurons, these findings may be significant for endocrine integration, which is important for reproductive behavior.

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Distinct Tissue-Specific Roles for Thyroid Hormone Receptors β and α1 in Regulation of Type 1 Deiodinase Expression

Molecular Endocrinology ◽

10.1210/mend.15.3.0605 ◽

2001 ◽

Vol 15 (3) ◽

pp. 467-475 ◽

Cited By ~ 4

Author(s):

Lori L. Amma ◽

Angel Campos-Barros ◽

Zhendong Wang ◽

Björn Vennström ◽

Douglas Forrest

Keyword(s):

Thyroid Hormone ◽

Hormone Receptors ◽

Critical Role ◽

Thyroid Hormone Receptors ◽

Minor Role ◽

Tissue Specific ◽

Mice Liver

Abstract Type 1 deiodinase (D1) metabolizes different forms of thyroid hormones to control levels of T3, the active ligand for thyroid hormone receptors (TR). The D1 gene is itself T3-inducible and here, the regulation of D1 expression by TRα1 and TRβ, which act as T3-dependent transcription factors, was investigated in receptor-deficient mice. Liver and kidney D1 mRNA and activity levels were reduced in TRβ−/− but not TRα1−/− mice. Liver D1 remained weakly T3 inducible in TRβ–/– mice whereas induction was abolished in double mutant TRα1–/–TRβ–/– mice. This indicates that TRβ is primarily responsible for regulating D1 expression whereas TRα1 has only a minor role. In kidney, despite the expression of both TRα1 and TRβ, regulation relied solely on TRβ, thus revealing a marked tissue restriction in TR isotype utilization. Although TRβ and TRα1 mediate similar functions in vitro, these results demonstrate differential roles in regulating D1 expression in vivo and suggest that tissue-specific factors and structural distinctions between TR isotypes contribute to functional specificity. Remarkably, there was an obligatory requirement for a TR, whether TRβ or TRα1, for any detectable D1 expression in liver. This suggests a novel paradigm of gene regulation in which the TR sets both basal expression and the spectrum of induced states. Physiologically, these findings suggest a critical role for TRβ in regulating the thyroid hormone status through D1-mediated metabolism.

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In Vitro Studies on Thyroid Hormone Receptors

Receptors and Hormone Action ◽

10.1016/b978-0-12-526303-0.50008-4 ◽

1978 ◽

pp. 35-74 ◽

Cited By ~ 22

Author(s):

HERBERT H. SAMUELS

Keyword(s):

Thyroid Hormone ◽

Hormone Receptors ◽

In Vitro Studies ◽

Thyroid Hormone Receptors

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Detection of thyroid hormone receptors in the olfactory system and brain of wild masu salmon, Oncorhynchus masou (Brevoort), during smolting by in vitro autoradiography

Aquaculture Research ◽

10.1111/are.1994.25.s2.171 ◽

1994 ◽

Vol 25 (S2) ◽

pp. 171-181 ◽

Cited By ~ 2

Author(s):

H. KUDO ◽

Y. TSUNEYOSHI ◽

M. NAGAE ◽

S. ADACHI ◽

K. YAMAUCHI ◽

...

Keyword(s):

Thyroid Hormone ◽

Olfactory System ◽

Hormone Receptors ◽

Masu Salmon ◽

Thyroid Hormone Receptors ◽

Oncorhynchus Masou ◽

In Vitro Autoradiography ◽

Masu Salmon Oncorhynchus Masou

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Do unliganded thyroid hormone receptors have physiological functions?

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0310009 ◽

2003 ◽

Vol 31 (1) ◽

pp. 9-20 ◽

Cited By ~ 37

Author(s):

O Chassande

Keyword(s):

Thyroid Hormone ◽

Hormone Receptors ◽

Target Genes ◽

Thyroid Hormone Receptors ◽

Intrinsic Activity ◽

Vertebrate Development ◽

Transcriptional Responses ◽

Embryonic And Fetal Development

Thyroid hormone (TH) is required for the development of vertebrates and exerts numerous homeostatic functions in adults. TH acts through nuclear receptors which control the transcription of target genes. Unliganded and liganded thyroid hormone receptors (TRs) have been shown to exert opposite effects on the transcription of target genes in vitro. However, the occurance of an aporeceptor activity in vivo and its potential physiological significance has not been clearly addressed. Several data generated using experimental hypothyroidism and thyrotoxicosis in wild type and TR knockout mice support the notion that apoTRs have an intrinsic activity in several tIssues. ApoTRs, and in particular TRalpha1, are predominant during the early stages of vertebrate development and must be turned into holoTRs for post-natal development to proceed normally. However, the absence of striking alterations of embryonic and fetal development in mice devoid of TRs indicates that apoTRs do not play a fundamental role. During development, as well as in adults, apoTRs rather appears as a system which increases the range of transcriptional responses to moderate variations of T3.

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