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Related Experiment Videos

Thyroid receptor alpha1 and alpha2 mutations in nonfunctioning pituitary tumors.

C J McCabe1, N J Gittoes, M C Sheppard

  • 1Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.

The Journal of Clinical Endocrinology and Metabolism
|February 18, 1999
PubMed
Summary

Nonfunctioning pituitary tumors show altered thyroid receptor (TR) expression. Researchers identified novel mutations in TRalpha, suggesting a role for these receptors in pituitary tumor growth.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Nonfunctioning pituitary tumors often display reduced thyroid receptor (TR) expression, potentially disrupting T3-mediated negative regulation of the glycoprotein hormone alpha-subunit.
  • Previous findings indicated reduced TR protein and TRbeta mRNA, but TRalpha mRNA levels were comparable to normal pituitaries, suggesting complex regulatory mechanisms.

Purpose of the Study:

  • To investigate potential mutations in thyroid receptor alpha (TRalpha) and thyroid receptor beta (TRbeta) coding and regulatory sequences in nonfunctioning pituitary tumors.
  • To explore the role of aberrant TR expression and potential mutations in the pathogenesis of pituitary tumors.

Main Methods:

  • Screening of TRalpha mRNA and TRbeta T3 response elements and ligand binding domains for sequence anomalies in pituitary tumor samples.

Related Experiment Videos

  • Sequencing of identified candidate fragments from TRalpha mRNA.
  • Comparison of sequences with published wild-type sequences.

    • Main Results:

    • Three novel missense mutations (ser45ile, lys370asn in TRalpha; ser377leu in TRalpha2) were identified in TRalpha mRNA.
    • One silent change in TRalpha mRNA was also noted.
    • No significant differences in TRbeta response elements or ligand binding domains were found between tumors and normal tissues.

    Conclusions:

    • Novel mutations in TRalpha may contribute to altered TR function in nonfunctioning pituitary tumors.
    • The functional significance of these TRalpha mutations requires further investigation to understand their role in pituitary cell growth control.