Signaling pathways of the LGR7 and LGR8 receptors determined by reporter genes

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Signaling

Background:

• Relaxin, a peptide hormone, mediates diverse physiological effects through its receptors, LGR7 and LGR8.
• The precise intracellular signaling cascades activated by relaxin family peptides remain incompletely understood.

Purpose of the Study:

• To elucidate the signaling pathways activated by human relaxin (H2) binding to LGR7 and insulin-like peptide 3 (INSL3) binding to LGR8.
• To investigate the role of cyclic AMP-dependent protein kinase A (cAMP-PKA) and mitogen-activated protein kinase (MAPK) pathways in LGR7/LGR8 signaling.

Main Methods:

• Utilized reporter gene technology to assess the activation of specific signaling pathways.
• Examined the activation of CRE (cAMP response element) and AP1 (activator protein 1) reporters.
• Compared the signaling responses induced by H2 relaxin and INSL3 on their respective receptors.

Main Results:

• The CRE reporter, indicative of cAMP-PKA and p38/JNK pathway activation, showed the strongest response.
• H2 relaxin treatment of LGR7 elicited a greater CRE reporter response compared to INSL3 treatment of LGR8.
• AP1 reporter activation, suggesting JNK pathway involvement, was observed to a lesser extent; other reporters remained unresponsive.

Conclusions:

• Ligand stimulation of LGR7 and LGR8 receptors predominantly engages the cAMP-PKA and p38/JNK signaling cascades.
• These findings provide crucial insights into the molecular mechanisms underlying relaxin family peptide actions.
• Reporter gene studies confirm the involvement of specific intracellular pathways in mediating receptor activation.