Analysis of Lgr4 function and development of anti-LGR4 antibody drug in gynecology

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Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) is a type of membrane receptor with a seven-transmembrane structure.We observed that Lgr4-/- female mice showed abnormal development of the Wolffian ducts, the appearance of male-like somatic cells in the ovaries. Lgr4-/- female mice exhibited masculinization similar to RSPO1-, beta-catenin-, and Wnt4-deficient mice. In the Lgr4-/- ovarian somatic cells, Lefl and Axin2 expression was reduced, which were target genes of Wnt-beta catenin signaling. On the other hand the androgen receptor (AR) expression in Wolffian ducts and ovarian somatic cells of Lgr4-/- female was increased. This study suggested that Lgr4 was critical to ovarian somatic cell specialization through the cooperative signaling of RSPOs and Wnt and involved the regulation of the AR expression in female reproductive organs.