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Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
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The Thyroid Gland01:23

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The thyroid gland is a small, butterfly-shaped gland located in the neck and covers the anterior surface of the trachea. The gland has two lateral lobes connected by a thin tissue mass called the isthmus. Internally, each lobe comprises many small spherical structures known as thyroid follicles, surrounded by a network of blood vessels.
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The Parathyroid Glands00:59

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The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Transoral Robotic Total Thyroidectomy and Bilateral Central Regional Lymph Node Dissection for Papillary Thyroid Carcinoma
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Two Cohorts, One Network: Consensus Master Regulators Orchestrating Papillary Thyroid Carcinoma.

Diana Tapia-Carrillo1, Octavio Zambada-Moreno2, Enrique Hernández-Lemus3

  • 1Escuela Nacional Preparatoria Plantel 9 "Pedro de Alba", Universidad Nacional Autónoma de Mexico, Mexico City 07300, Mexico.

International Journal of Molecular Sciences
|November 27, 2025
PubMed
Summary

This study identifies key transcriptional master regulators (TMRs) driving papillary thyroid carcinoma (PTC) by analyzing gene expression data. These findings reveal the complex signaling networks involved in thyroid cancer progression and offer targets for new therapies.

Keywords:
TGF-β signalingestrogen signalinggene regulatory networksmeta-analysismolecular endocrinologypapillary thyroid carcinomatranscriptional master regulators

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Area of Science:

  • Endocrinology
  • Genomics
  • Oncology
  • Bioinformatics

Background:

  • Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy.
  • The transcriptional hierarchies governing PTC progression are not well understood.
  • Identifying master regulators is crucial for understanding tumor development.

Purpose of the Study:

  • To identify consensus transcriptional master regulators (TMRs) driving PTC.
  • To delineate the transcriptional and hormonal circuitry underlying thyroid tumorigenesis.
  • To provide a regulatory framework for biomarker-driven therapies.

Main Methods:

  • Integrated gene-expression profiles from two independent cohorts (TCGA-THCA and GSE33630).
  • Reconstructed regulon networks using ARACNe-AP and inferred TMR activity with VIPER.
  • Performed Fisher's meta-analysis for cross-cohort evidence integration.

Main Results:

  • Identified 50 shared TMRs, primarily from Zinc Finger, Forkhead, ETS, and nuclear receptor families.
  • Highlighted key upstream regulators including PBX4, GATAD2A, BHLHE40, HEY2, and TEAD4.
  • Revealed activation of NOTCH, MAPK, PI3K, TGF-β signaling, and estrogen-response programs, including a novel role for SMAD9 in TGF-β signaling.

Conclusions:

  • Delineated the transcriptional and hormonal circuitry of thyroid tumorigenesis.
  • Established a regulatory framework for developing network activity-based biomarkers and therapies for PTC.
  • Uncovered potential therapeutic targets within the identified signaling pathways.