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Thyroid hormone regulates the oxytocin gene.
R A Adan1, J J Cox, J P van Kats
1Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
The Journal of Biological Chemistry
|February 25, 1992
Summary
Thyroid hormone (T3) directly regulates oxytocin (OT) gene expression by binding to a specific thyroid hormone-response element. This finding reveals T3 as a physiological regulator of OT, impacting OT levels in the brain and blood.
Area of Science:
- Endocrinology
- Molecular Biology
- Neuroscience
Background:
- Oxytocin (OT) plays crucial roles in social behavior and physiological functions.
- Transcriptional regulation of the OT gene by various factors is essential for controlling its expression.
- The influence of endocrine factors, particularly thyroid hormone, on OT gene regulation requires further elucidation.
Purpose of the Study:
- To investigate the role of endocrine factors, specifically thyroid hormone, in the transcriptional regulation of the oxytocin (OT) gene.
- To identify the specific DNA elements within the OT gene promoter responsible for thyroid hormone responsiveness.
- To explore potential interactions between thyroid hormone receptors and estrogen receptors in regulating OT gene expression.
Main Methods:
- Heterologous expression systems using luciferase reporter gene assays in P19 embryonal carcinoma (EC) and MCF-7 breast tumor cells.
- Co-transfection with expression vectors for thyroid hormone receptors.
- 5' deletion mutant analysis of the rat OT gene promoter.
- Gel retardation assays to assess protein-DNA binding.
- In vivo experiments in rats involving thyroid hormone administration.
Main Results:
- Thyroid hormone (T3) significantly stimulated both rat and human OT promoter activity (10-fold and 5-fold, respectively).
- Thyroid hormone responsiveness was localized to two distinct regions within the rat OT gene promoter (-195/-172 and -172/-148).
- Specific binding of thyroid hormone receptor alpha to the -172/-148 element was observed, which contains TGACC motifs crucial for T3 responsiveness.
- Thyroid hormone treatment increased hypothalamic OT mRNA, pituitary OT content, and blood OT levels in rats.
- Negative interactions were observed between thyroid hormone and estrogen receptors.
Conclusions:
- Thyroid hormone acts as a physiological regulator of oxytocin gene expression.
- T3 directly stimulates OT promoter activity via interaction with a thyroid hormone-response element.
- The identified thyroid hormone-response element in the OT gene is critical for mediating T3's regulatory effects.
- Interactions between thyroid hormone and estrogen receptors may negatively impact OT gene regulation.