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Updated: Aug 11, 2026
08:19
Quantitative Comparison of cis-Regulatory Element (CRE) Activities in Transgenic Drosophila melanogaster
Published on: December 19, 2011
A dominant negative CREB (cAMP response element-binding protein) isoform inhibits thyrocyte growth, thyroid-specific
L Q Nguyen1, P Kopp, F Martinson
1Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.
Molecular Endocrinology (Baltimore, Md.)
|September 8, 2000
Summary
The cAMP response element binding protein (CREB) is crucial for thyroid function. Inhibiting CREB in mice led to hypothyroidism, impaired thyroid growth, and failed follicular cell differentiation.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Cyclic adenosine monophosphate (cAMP) mediates thyroid-stimulating hormone (TSH) effects on thyroid follicular cells.
- The role of cAMP response element binding protein (CREB) in thyroid regulation requires in vivo investigation.
Purpose of the Study:
- To determine the functional significance of CREB in thyroid follicular cell regulation in vivo.
- To investigate the impact of dominant-negative CREB expression on thyroid gland development and function.
Main Methods:
- Generation of transgenic mice with thyroid-specific expression of a dominant-negative (DN) CREB isoform.
- Assessment of thyroid gland histology, serum hormone levels (TSH, T4, T3), and gene expression via semiquantitative RT-PCR.
Main Results:
- Transgenic mice displayed severe growth retardation and primary hypothyroidism with elevated TSH and low T4/T3 levels.
- Thyroid glands showed poorly developed, heterogeneous follicles, diminished colloid, and ciliated epithelial cells, indicating differentiation failure.
- DN CREB inhibited key thyroid genes (thyroglobulin, thyroperoxidase, TSH receptor) and altered thyroid transcription factors (Pax-8, TTF-1, TTF-2).
Conclusions:
- CREB plays a critical role in regulating thyroid follicular cell proliferation, differentiation, and function in vivo.
- Disruption of CREB function leads to significant thyroid abnormalities and hypothyroidism.
- These findings highlight CREB as a key regulator in thyroid homeostasis.
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