Rapid Screening of Glucocorticoid Receptor (GR) Effectors Using Cortisol-Detecting Sensor Cells

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Cortisol is a key stress and anti-inflammatory hormone.
• Abnormal cortisol levels necessitate monitoring and drug candidate screening.
• Existing screening methods may lack efficiency in complex cellular environments.

Purpose of the Study:

• To develop a novel cell-based sensor for rapid screening of cortisol and its analogues.
• To identify novel glucocorticoid receptor (GR) effectors from natural products.
• To characterize L-limonene as a potential therapeutic agent.

Main Methods:

• Development of a cell-based sensor utilizing split intein-mediated conditional protein splicing (CPS).
• The sensor system employs a GR-split intein fusion to detect target molecules.
• Screening of essential oil extracts and their components for GR effector activity.

Main Results:

• The sensor cells demonstrated high sensitivity and specificity in discriminating cortisol analogues.
• Peppermint oil was identified as a source of GR effectors.
• L-limonene and L-menthol were identified as major GR effectors in peppermint oil.
• L-limonene was characterized as a selective GR agonist (SEGRA).

Conclusions:

• The novel cell-based sensor enables efficient screening of cortisol and its analogues.
• L-limonene is a promising selective GR agonist with potential anti-inflammatory applications.
• This approach facilitates the discovery of natural compounds with therapeutic potential.