Triiodothyronine rapidly decreases transcription of the thyrotropin subunit genes in thyrotropic tumor explants

Endocrinology
|November 1, 1985
PubMed

Insights

The thyroid hormone T3 directly suppresses thyroid-stimulating hormone (TSH) beta and alpha-subunit mRNA synthesis in thyrotropes. This direct action occurs without requiring new protein synthesis, indicating T3

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Gene Regulation

Background:

  • Thyroid hormone (T3) plays a crucial role in regulating thyroid-stimulating hormone (TSH) production.
  • The precise molecular mechanisms by which T3 affects TSH subunit gene expression are not fully elucidated.
  • Thyrotropic tumor cells provide a model system to study direct hormonal effects on TSH gene regulation.

Purpose of the Study:

  • To investigate the direct impact of the thyroid hormone T3 on the synthesis of TSH beta and alpha-subunit mRNA.
  • To determine if protein synthesis is required for T3-mediated suppression of TSH subunit gene transcription.
  • To correlate T3's transcriptional effects with its nuclear receptor binding kinetics.

Main Methods:

  • Treatment of TtT 97 thyrotropic tumor explants with T3.
  • Isolation of nuclei and in vitro RNA synthesis labeling with [alpha-32P]UTP.
  • Quantification of newly synthesized TSH beta and alpha-subunit mRNA via cDNA hybridization.
  • Assessment of cycloheximide's effect on T3-mediated gene regulation.

Main Results:

  • T3 significantly decreased TSH beta and alpha-subunit mRNA synthesis rates in a time-dependent manner.
  • Suppression of mRNA synthesis by T3 correlated with T3 nuclear receptor binding.
  • Decreases in mRNA synthesis preceded changes in steady-state mRNA or protein levels.
  • Cycloheximide did not alter T3's suppressive effects on transcription or mRNA levels.

Conclusions:

  • T3 directly suppresses TSH beta and alpha-subunit mRNA synthesis at the transcriptional level in thyrotropes.
  • Protein synthesis is not required for the immediate T3-induced downregulation of TSH subunit gene transcription.
  • T3 directly modulates TSH subunit gene expression, likely acting at the gene level.

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