Resurgence of an Inborn Attraction for Animate Objects via Thyroid Hormone T3

For inexperienced brains, some stimuli are more attractive than others. Human neonates and newly hatched chicks preferentially orient towards face-like stimuli, biological motion, and objects changing speed. In chicks, this enhances exposure to social partners, and subsequent attachment trough filial imprinting. Early preferences are not steady. For instance, preference for stimuli changing speed fades away after 2 days in chicks. To understand the physiological mechanisms underlying these transient responses, we tested whether early preferences for objects changing speed can be promoted by thyroid hormone 3,5,3′-triiodothyronine (T3). This hormone determines the start of imprinting’s sensitive period. We found that the preference for objects changing speed can be re-established in female chicks treated with T3. Moreover, day-1 chicks treated with an inhibitor of endogenous T3 did not show any preference. These results suggest that the time windows of early predispositions and of sensitive period for imprinting are controlled by the same molecular mechanisms.

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Resurgence of a perinatal attraction for animate objects via thyroid hormone T3

10.1101/2020.11.16.384289 ◽

2020 ◽

Author(s):

Elena Lorenzi ◽

Bastien S. Lemaire ◽

Elisabetta Versace ◽

Toshiya Matsushima ◽

Giorgio Vallortigara

Keyword(s):

Thyroid Hormone ◽

Biological Motion ◽

Molecular Mechanisms ◽

Time Windows ◽

Sensitive Period ◽

High Plasticity ◽

Transient Responses ◽

Physiological Mechanisms ◽

Filial Imprinting ◽

Human Neonates

SummaryFor inexperienced brains, some stimuli are more attractive than others. Human neonates and newly-hatched chicks preferentially orient towards face-like stimuli, biological motion, and objects changing speed. In chicks, this enhances exposure to social partners, and subsequent attachment trough filial imprinting. Early preferences are not steady. The preference for stimuli changing speed fades away after three days in chicks. To understand the physiological mechanisms underlying these transient responses, we tested whether the early preferences for objects changing speed can be promoted by thyroid hormone 3,5,3’-triiodothyronine (T3). This hormone determines the start of imprinting’s sensitive period. We found that the preference for objects changing speed can be re-established in female chicks treated with T3. Moreover, day-one chicks treated with an inhibitor of endogenous T3 did not show any preference. These results suggest that the time windows of early predispositions and of high plasticity are controlled by the same molecular mechanisms.

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Wnt-2b in the intermediate hyperpallium apicale of the telencephalon is critical for the thyroid hormone-mediated opening of the sensitive period for filial imprinting in domestic chicks (Gallus gallus domesticus)

Hormones and Behavior ◽

10.1016/j.yhbeh.2018.05.011 ◽

2018 ◽

Vol 102 ◽

pp. 120-128 ◽

Cited By ~ 7

Author(s):

Shinji Yamaguchi ◽

Naoya Aoki ◽

Toshiya Matsushima ◽

Koichi J. Homma

Keyword(s):

Thyroid Hormone ◽

Gallus Gallus ◽

Gallus Domesticus ◽

Sensitive Period ◽

Gallus Gallus Domesticus ◽

Domestic Chicks ◽

Filial Imprinting

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Molecular mechanisms of sex-dependent thyroid hormone action on target tissues

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0034-1372162 ◽

2014 ◽

Vol 122 (03) ◽

Author(s):

H Rakov ◽

K Engels ◽

D Zwanziger ◽

M Renders ◽

K Brix ◽

...

Keyword(s):

Thyroid Hormone ◽

Molecular Mechanisms ◽

Hormone Action ◽

Thyroid Hormone Action

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The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

International Journal of Molecular Sciences ◽

10.3390/ijms22020803 ◽

2021 ◽

Vol 22 (2) ◽

pp. 803

Author(s):

Giuseppina Emanuela Grieco ◽

Noemi Brusco ◽

Giada Licata ◽

Daniela Fignani ◽

Caterina Formichi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Metabolic Disorders ◽

Molecular Mechanisms ◽

Β Cell ◽

Physiological Mechanisms ◽

Effective Strategies ◽

Chronic Hyperglycaemia ◽

Shed Light

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.

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Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene

Biochemical Journal ◽

10.1042/bj20090671 ◽

2010 ◽

Vol 427 (1) ◽

pp. 161-169 ◽

Cited By ~ 15

Author(s):

Mariko Ishiguro ◽

Hironori Yamamoto ◽

Masashi Masuda ◽

Mina Kozai ◽

Yuichiro Takei ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Molecular Mechanisms ◽

Hormone Receptors ◽

Critical Role ◽

Serum Phosphate ◽

Luciferase Assay ◽

Mobility Shift ◽

Intron 1 ◽

Sodium Dependent

The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3′,5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner.

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Desethylamiodarone antagonizes the effect of thyroid hormone at the molecular level

Acta Endocrinologica ◽

10.1530/eje.0.1450059 ◽

2001 ◽

pp. 59-64 ◽

Cited By ~ 18

Author(s):

F Bogazzi ◽

L Bartalena ◽

S Brogioni ◽

A Burelli ◽

F Raggi ◽

...

Keyword(s):

Thyroid Hormone ◽

Molecular Mechanisms ◽

Thyroid Hormone Receptor ◽

Molecular Level ◽

Inhibitory Effect ◽

Mobility Shift ◽

Down Regulation ◽

Nih3t3 Cells ◽

Peripheral Tissues

OBJECTIVE: To evaluate the molecular mechanisms of the inhibitory effects of amiodarone and its active metabolite, desethylamiodarone (DEA) on thyroid hormone action. MATERIALS AND METHODS: The reporter construct ME-TRE-TK-CAT or TSHbeta-TRE-TK-CAT, containing the nucleotide sequence of the thyroid hormone response element (TRE) of either malic enzyme (ME) or TSHbeta genes, thymidine kinase (TK) and chloramphenicol acetyltransferase (CAT) was transiently transfected with RSV-TRbeta into NIH3T3 cells. Gel mobility shift assay (EMSA) was performed using labelled synthetic oligonucleotides containing the ME-TRE and in vitro translated thyroid hormone receptor (TR)beta. RESULTS: Addition of 1 micromol/l T4 or T3 to the culture medium increased the basal level of ME-TRE-TK-CAT by 4.5- and 12.5-fold respectively. Amiodarone or DEA (1 micromol/l) increased CAT activity by 1.4- and 3.4-fold respectively. Combination of DEA with T4 or T3 increased CAT activity by 9.4- and 18.9-fold respectively. These data suggested that DEA, but not amiodarone, had a synergistic effect with thyroid hormone on ME-TRE, rather than the postulated inhibitory action; we supposed that this was due to overexpression of the transfected TR into the cells. When the amount of RSV-TRbeta was reduced until it was present in a limited amount, allowing competition between thyroid hormone and the drug, addition of 1 micromol/l DEA decreased the T3-dependent expression of the reporter gene by 50%. The inhibitory effect of DEA was partially due to a reduced binding of TR to ME-TRE, as assessed by EMSA. DEA activated the TR-dependent down-regulation by the negative TSH-TRE, although at low level (35% of the down-regulation produced by T3), whereas amiodarone was ineffective. Addition of 1 micromol/l DEA to T3-containing medium reduced the T3-TR-mediated down-regulation of TSH-TRE to 55%. CONCLUSIONS: Our results demonstrate that DEA, but not amiodarone, exerts a direct, although weak, effect on genes that are regulated by thyroid hormone. High concentrations of DEA antagonize the action of T3 at the molecular level, interacting with TR and reducing its binding to TREs. This effect may contribute to the hypothyroid-like effect observed in peripheral tissues of patients receiving amiodarone treatment.

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Regulation of β myosin heavy chain, c-myc and c-fos proto-oncogenes in thyroid hormone-induced hypertrophy of the rat myocardium

Clinical Science ◽

10.1042/cs0840061 ◽

1993 ◽

Vol 84 (1) ◽

pp. 61-67 ◽

Cited By ~ 9

Author(s):

N. K. Green ◽

M. D. Gammage ◽

J. A. Franklyn ◽

A. M. Heagerty ◽

M. C. Sheppard

Keyword(s):

Thyroid Hormone ◽

Right Ventricular ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Molecular Mechanisms ◽

Left Ventricular ◽

Transcriptional Level ◽

Messenger Rnas ◽

Hypertrophic Response ◽

Left And Right

1. In order to investigate the molecular mechanisms determining the hypertrophic response of the ventricular myocardium to thyroid hormone administration, changes in left and right ventricular expression of the c-myc, c-fos and H-ras proto-oncogenes in response to treatment with 3,3′,5-tri-iodothyronine were defined. 2. Adult female Wistar rats were treated with daily subcutaneous injections of 3,3′,5-tri-iodothyronine (50 μg) for 1, 3, 7 or 14 days (n = 6 in each treatment group) and the results from 3,3′,5-tri-iodothyronine-treated animals were compared with those obtained from untreated controls (n = 6). Changes in the weight of the left and right ventricles in response to 3,3′,5-tri-iodothyronine treatment were measured; changes in expression of the c-myc, c-fos and H-ras proto-oncogenes were determined in parallel by measurement of specific messenger RNAs by Northern and dot hybridization, as well as changes in expression of β myosin heavy chain messenger RNA. 3. Treatment with 3,3′,5-tri-iodothyronine resulted in increases in both left and right ventricular weights after 3 days, an effect maintained up to 14 days. Despite an increase in left ventricular weight, levels of β myosin heavy chain, c-myc, c-fos and H-ras mRNAs in the left ventricle were unchanged; in contrast, an increase in right ventricular weight was associated with increased expression of β myosin heavy chain, c-myc and c-fos messenger RNAs. 4. These specific ventricular changes in gene expression, in the face of a hypertrophic response of both ventricles to 3,3′,5-tri-iodothyronine, suggest that the cardiac growth response to thyroid hormones reflects the well-documented secondary haemodynamic influences rather than direct gene regulatory actions of 3,3′,5-tri-iodothyronine at the transcriptional level on the genes studied. Changes in right ventricular proto-oncogene and β myosin heavy chain expression may in turn reflect an increase in right ventricular pressure load.

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Skeletal Muscle Wasting: The Estrogen Side of Sexual Dimorphism

AJP Cell Physiology ◽

10.1152/ajpcell.00333.2021 ◽

2021 ◽

Author(s):

Shawna L. McMillin ◽

Everett C. Minchew ◽

Dawn A. Lowe ◽

Espen E. Spangenburg

Keyword(s):

Sex Differences ◽

Sexual Dimorphism ◽

Molecular Mechanisms ◽

Muscle Wasting ◽

Physiological Mechanisms ◽

Skeletal Muscle Wasting ◽

Muscle Biology ◽

Experimental Approaches ◽

The Impact ◽

Equal Efficacy

The importance of defining sex differences across various biological and physiological mechanisms is more pervasive now than it has been over the last 15-20 years. As the muscle biology field pushes to identify small molecules and interventions to prevent, attenuate or even reverse muscle wasting, we must consider the effect of sex as a biological variable. It should not be assumed that a therapeutic will affect males and females with equal efficacy or equivalent target affinities under conditions where muscle wasting is observed. With that said, it is not surprising to find that we have an unclear or even a poor understanding of the effects of sex or sex hormones on muscle wasting conditions. Although recent investigations are beginning to establish experimental approaches that will allow investigators to assess the impact of sex-specific hormones on muscle wasting, the field still has not established enough published scientific tools that will allow the field to rigorously address critical hypotheses. Thus, the purpose of this review is to assemble a current summary of knowledge in the area of sexual dimorphism driven by estrogens with an effort to provide insights to interested physiologists on necessary considerations when trying to assess models for potential sex differences in cellular and molecular mechanisms of muscle wasting.

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