scholarly journals The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis

2011 ◽  
Vol 96 (2) ◽  
pp. 557-557
Author(s):  
Inna Astapova ◽  
Kristen R. Vella ◽  
Preeti Ramadoss ◽  
Kaila A. Holtz ◽  
Benjamin A. Rodwin ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Sensitivity ◽  
Set Point ◽  
Nuclear Receptor Corepressor ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis

2011 ◽  
Vol 25 (2) ◽  
pp. 212-224 ◽  
Author(s):  
Inna Astapova ◽  
Kristen R. Vella ◽  
Preeti Ramadoss ◽  
Kaila A. Holtz ◽  
Benjamin A. Rodwin ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Sensitivity ◽  
Set Point ◽  
Nuclear Receptor Corepressor ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals The Nuclear Receptor Corepressor (NCoR) Controls Thyroid Hormone Sensitivity and the Set Point of the Hypothalamic-Pituitary-Thyroid Axis

2011 ◽  
Vol 32 (1) ◽  
pp. 153-153
Author(s):  
Inna Astapova ◽  
Kristen R. Vella ◽  
Preeti Ramadoss ◽  
Kaila A. Holtz ◽  
Benjamin A. Rodwin ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptor ◽  
Hormone Sensitivity ◽  
Set Point ◽  
Nuclear Receptor Corepressor ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals Neuropeptide Y1 and Y5 Receptors Mediate the Effects of Neuropeptide Y on the Hypothalamic-Pituitary-Thyroid Axis

Endocrinology ◽  
2002 ◽  
Vol 143 (12) ◽  
pp. 4513-4519 ◽  
Author(s):  
Csaba Fekete ◽  
Sumit Sarkar ◽  
William M. Rand ◽  
John W. Harney ◽  
Charles H. Emerson ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Paraventricular Nucleus ◽  
Receptor Agonist ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Ad Libitum ◽  
Thyroid Hormone Levels ◽  
Hpt Axis

Abstract Neuropeptide Y (NPY) is one of the most important hypothalamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously inhibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fasting. To identify the specific NPY receptor subtypes involved in the action of NPY on the HPT axis, we studied the effects of the highly selective Y1 ([Phe7,Pro34]pNPY) and Y5 ([chicken pancreatic polypeptide1–7, NPY19–23, Ala31, Aib32 (aminoisobutyric acid), Q34]human pancreatic polypeptide) receptor agonists on circulating thyroid hormone levels and proTRH mRNA in hypophysiotropic neurons of the hypothalamic paraventricular nucleus. The peptides were administered continuously by osmotic minipump into the cerebrospinal fluid (CSF) over 3 d in ad libitum-fed animals and animals pair-fed to artificial CSF (aCSF)-infused controls. Both Y1 and Y5 receptor agonists nearly doubled food intake compared with that of control animals receiving aCSF, similar to the effect observed for NPY. NPY, Y1, and Y5 receptor agonist administration suppressed circulating levels of thyroid hormones (T3 and T4) and resulted in inappropriately normal or low TSH levels. These alterations were also associated with significant suppression of proTRH mRNA in the paraventricular nucleus, particularly in the Y1 receptor agonist-infused group [aCSF, NPY, Y1, and Y5 (density units ± sem), 97.2 ± 8.6, 39.6 ± 8.4, 19.9 ± 1.9, and 44.6 ± 8.4]. No significant differences in thyroid hormone levels, TSH, or proTRH mRNA were observed between the agonist-infused FSanimals eating ad libitum and the agonist-infused animals pair-fed with vehicle-treated controls. These data confirm the importance of both Y1 and Y5 receptors in the NPY-mediated increase in food consumption and demonstrate that both Y1 and Y5 receptors can mediate the inhibitory effects of NPY on the HPT axis.

scholarly journals The TRH Gene Is Regulated by Thyroid Hormone at the Level of Transcription in Vivo

2010 ◽  
Vol 31 (1) ◽  
pp. 136-136
Author(s):  
Michelle L. Sugrue ◽  
Kristen R. Vella ◽  
Crystal Morales ◽  
Marisol E. Lopez ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Genomic Region ◽  
Model System ◽  
Model Systems ◽  
In Vivo Model ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Normal Production

ABSTRACT The expression of the TRH gene in the paraventricular nucleus (PVH) of the hypothalamus is required for the normal production of thyroid hormone (TH) in rodents and humans. In addition, the regulation of TRH mRNA expression by TH, specifically in the PVH, ensures tight control of the set point of the hypothalamic-pituitary-thyroid axis. Although many studies have assumed that the regulation of TRH expression by TH is at the level of transcription, there is little data available to demonstrate this. We used two in vivo model systems to show this. In the first model system, we developed an in situ hybridization (ISH) assay directed against TRH heteronuclear RNA to measure TRH transcription directly in vivo. We show that in the euthyroid state, TRH transcription is present both in the PVH and anterior/lateral hypothalamus. In the hypothyroid state, transcription is activated in the PVH only and can be shut off within 5 h by TH. In the second model system, we employed transgenic mice that express the Cre recombinase under the control of the genomic region containing the TRH gene. Remarkably, TH regulates Cre expression in these mice in the PVH only. Taken together, these data affirm that TH regulates TRH at the level of transcription in the PVH only and that genomic elements surrounding the TRH gene mediate its regulation by T3. Thus, it should be possible to identify the elements within the TRH locus that mediate its regulation by T3 using in vivo approaches.

Absence of thyroid hormone receptor β–retinoid X receptor interactions in auditory function and in the pituitary–thyroid axis

Neuroreport ◽  
1998 ◽  
Vol 9 (13) ◽  
pp. 2933-2937 ◽  
Author(s):  
Angel Campos Barros ◽  
Lawrence C. Erway ◽  
Wojciech Krezel ◽  
Tom Curran ◽  
Philippe Kastner ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Retinoid X Receptor ◽  
Auditory Function ◽  
Receptor Interactions ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Thyroid Hormone Receptor Β

scholarly journals Minireview: The Neural Regulation of the Hypothalamic-Pituitary-Thyroid Axis

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4128-4135 ◽  
Author(s):  
Ricardo H. Costa-e-Sousa ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Adult Life ◽  
Feedback System ◽  
Primary Hypothyroidism ◽  
Neural Regulation ◽  
Pituitary Thyroid Axis ◽  
Genes Encoding ◽  
Thyroid Axis ◽  
Hpt Axis

Thyroid hormone (TH) signaling plays an important role in development and adult life. Many organisms may have evolved under selective pressure of exogenous TH, suggesting that thyroid hormone signaling is phylogenetically older than the systems that regulate their synthesis. Therefore, the negative feedback system by TH itself was probably the first mechanism of regulation of circulating TH levels. In humans and other vertebrates, it is well known that TH negatively regulates its own production through central actions that modulate the hypothalamic-pituitary-thyroid (HPT) axis. Indeed, primary hypothyroidism leads to the up-regulation of the genes encoding many key players in the HPT axis, such as TRH, type 2 deiodinase (dio2), pyroglutamyl peptidase II (PPII), TRH receptor 1 (TRHR1), and the TSH α- and β-subunits. However, in many physiological circumstances, the activity of the HPT axis is not always a function of circulating TH concentrations. Indeed, circadian changes in the HPT axis activity are not a consequence of oscillation in circulating TH levels. Similarly, during reduced food availability, several components of the HPT axis are down-regulated even in the presence of lower circulating TH levels, suggesting the presence of a regulatory pathway hierarchically higher than the feedback system. This minireview discusses the neural regulation of the HPT axis, focusing on both TH-dependent and -independent pathways and their potential integration.

scholarly journals Effects of Maternal Levels of Thyroid Hormone (TH) on the Hypothalamus-Pituitary-Thyroid Set Point: Studies in TH Receptor β Knockout Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5305-5312 ◽  
Author(s):  
Manuela Alonso ◽  
Charles Goodwin ◽  
XiaoHui Liao ◽  
David Page ◽  
Samuel Refetoff ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Elevated Serum ◽  
The Other ◽  
Long Term Effects ◽  
Intrauterine Environment ◽  
Set Point ◽  
Other Hand ◽  
Wild Type Phenotype ◽  
Pituitary Thyroid Axis ◽  
Serum Tsh

A level of thyroid hormone (TH) in agreement with the tissue requirements is essential for vertebrate embryogenesis and fetal maturation. In this study we evaluate the immediate and long-term effects of incongruent intrauterine TH levels between mother and fetus using the TH receptor (TR) β−/− knockout mouse as a model. We took advantage of the fact that the TRβ−/− females have elevated serum TH but are not thyrotoxic due to resistance to TH. We used crosses between heterozygotes with wild-type phenotype (TRβ+/−) males and TRβ−/− females, with a hyperiodothyroninemic (high T4 and T3 levels) intrauterine environment (TH congruent with the TRβ−/− fetus and excessive for the TRβ+/− fetus), and reciprocal crosses between TRβ−/− males and TRβ+/− females, providing a euiodothyroninemic intrauterine environment. We found that TRβ−/− dams had reduced litter sizes and pups with lower birth weight but preserved the mendelian TRβ−/− to TRβ+/− ratio at birth, indicating that the incongruous TH levels did not decrease intrauterine survival of a specific genotype. The results of studies in newborns demonstrate that TRβ+/− pups born to TRβ−/− dams have persistent suppression of serum TSH without a peak. On the other hand, TRβ−/− pups born to TRβ+/− dams have lower serum TSH at birth and a tendency to peak higher, compared with TRβ−/− pups born to TRβ−/− dams. The studies in the adult progeny demonstrate that TRβ+/− mice born to TRβ−/− dams and, thus, exposed to higher intrauterine TH levels, have greater resistance to TH at the level of the pituitary when stimulated with TRH. On the other hand, TRβ−/− mice born to TRβ+/− dams and, thus, deprived of TH in uterine life, were more sensitive to TH when similarly stimulated with TRH. Thus, TH exposure in utero has an effect on the regulatory set point of the hypothalamus-pituitary-thyroid axis, which can be seen early in life and persists into adulthood.

scholarly journals The Thyrotropin-Releasing Hormone Gene Is Regulated by Thyroid Hormone at the Level of Transcription in Vivo

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 793-801 ◽  
Author(s):  
Michelle L. Sugrue ◽  
Kristen R. Vella ◽  
Crystal Morales ◽  
Marisol E. Lopez ◽  
Anthony N. Hollenberg
Keyword(s):  
Thyroid Hormone ◽  
Genomic Region ◽  
Model System ◽  
Model Systems ◽  
In Vivo Model ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Normal Production

The expression of the TRH gene in the paraventricular nucleus (PVH) of the hypothalamus is required for the normal production of thyroid hormone (TH) in rodents and humans. In addition, the regulation of TRH mRNA expression by TH, specifically in the PVH, ensures tight control of the set point of the hypothalamic-pituitary-thyroid axis. Although many studies have assumed that the regulation of TRH expression by TH is at the level of transcription, there is little data available to demonstrate this. We used two in vivo model systems to show this. In the first model system, we developed an in situ hybridization (ISH) assay directed against TRH heteronuclear RNA to measure TRH transcription directly in vivo. We show that in the euthyroid state, TRH transcription is present both in the PVH and anterior/lateral hypothalamus. In the hypothyroid state, transcription is activated in the PVH only and can be shut off within 5 h by TH. In the second model system, we employed transgenic mice that express the Cre recombinase under the control of the genomic region containing the TRH gene. Remarkably, TH regulates Cre expression in these mice in the PVH only. Taken together, these data affirm that TH regulates TRH at the level of transcription in the PVH only and that genomic elements surrounding the TRH gene mediate its regulation by T3. Thus, it should be possible to identify the elements within the TRH locus that mediate its regulation by T3 using in vivo approaches.

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