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Regulation of glycoprotein hormone alpha-subunit gene expression
R A Maurer1, K E Kim, W E Schoderbek
1Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
Recent Progress in Hormone Research
|November 5, 1999
Summary
Regulated expression of glycoprotein hormone alpha-subunit genes is crucial for hormone biosynthesis. This study identifies key DNA elements and transcription factors, including GnRH-RE and LH-2, involved in alpha-subunit gene regulation via the MAPK pathway.
Area of Science:
- Molecular Endocrinology
- Gene Regulation
- Signal Transduction
Background:
- Regulated expression of glycoprotein hormone subunit genes is essential for producing key hormones like LH, FSH, TSH, and hCG.
- Understanding the molecular mechanisms controlling the common alpha-subunit gene is critical for reproductive and thyroid health.
Purpose of the Study:
- To identify DNA elements and transcription factors regulating the common alpha-subunit gene.
- To elucidate the signaling pathways, including the MAPK cascade, involved in GnRH-stimulated alpha-subunit expression.
Main Methods:
- Clustered point mutation analysis to identify functional DNA elements.
- Reporter gene assays to assess promoter activity and response to GnRH.
- Investigation of the mitogen-activated protein kinase (MAPK) pathway.
- Cloning and characterization of transcription factors interacting with regulatory elements.
Main Results:
- Two key DNA elements, GnRH-response element (GnRH-RE) and pituitary glycoprotein hormone basal element (PGBE), were identified.
- GnRH-RE mediates GnRH-stimulated expression and binds Ets transcription factors.
- MAPK pathway activation is necessary and sufficient for GnRH-induced alpha-subunit gene transcription.
- A LIM-homeodomain transcription factor, LH-2, was cloned and shown to bind PGBE, activating basal expression.
Conclusions:
- The study identified critical cis-acting elements (GnRH-RE, PGBE) and trans-acting factors (Ets family, LH-2) governing alpha-subunit gene transcription.
- The MAPK pathway plays a crucial role in mediating GnRH-stimulated alpha-subunit expression.
- LH-2 is a key factor responsible for basal expression of the alpha-subunit gene, contributing to the understanding of glycoprotein hormone regulation.