Related Experiment Video

Updated: Jun 28, 2025

Demonstrating a Linear Relationship Between Vascular Endothelial Growth Factor and Luteinizing Hormone in Kidney Cortex Extracts
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Published on: January 22, 2020

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An intracellular VHH targeting the Luteinizing Hormone receptor modulates G protein-dependent signaling and

Camille Gauthier1, Pauline Raynaud1, Frédéric Jean-Alphonse2

  • 1INRAE, CNRS, Université de Tours, PRC, 37380, Nouzilly, France.

Molecular and Cellular Endocrinology
|April 15, 2024
PubMed

Luteinizing hormone (LH) is essential for reproduction, controlling ovulation and steroidogenesis. Its receptor (LHR) recruits various transducers leading to the activation of a complex signaling network. We recently identified iPRC1, the first variable fragment from heavy-chain-only antibody (VHH) interacting with intracellular loop 3 (ICL3) of the follicle-stimulating hormone receptor (FSHR). Because of the high sequence similarity of the human FSHR and LHR (LHCGR), here we examined the ability of the iPRC1 intra-VHH to modulate LHCGR activity. In this study, we demonstrated that iPRC1 binds LHCGR, to a greater extent when the receptor was stimulated by the hormone. In addition, it decreased LH-induced cAMP production, cAMP-responsive element-dependent transcription, progesterone and testosterone production. These impairments are not due to Gs nor β-arrestin recruitment to the LHCGR. Consequently, iPRC1 is the first intra-VHH to bind and modulate LHCGR biological activity, including steroidogenesis. It should help further understand signaling mechanisms elicited at this receptor and their outcomes on reproduction.

Keywords:
Cell signalingG protein-coupled receptorIntracellular VHHLHRReproductionSteroidogenesis

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