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

富亮氨酸重复-含g蛋白偶联受体4 （LGR4）是一类具有七跨膜结构的膜受体。我们观察到Lgr4-/-雌性小鼠的沃尔夫管发育异常，卵巢内出现雄性样体细胞。Lgr4-/-雌性小鼠表现出与RSPO1-、β -catenin-和wnt4缺陷小鼠相似的雄性化。在Lgr4-/-卵巢体细胞中，wnt - β - catenin信号通路的靶基因Lefl和Axin2表达降低。另一方面，Lgr4-/-雌性狼管和卵巢体细胞中的雄激素受体（AR）表达增加。本研究提示Lgr4通过RSPOs和Wnt的协同信号传导对卵巢体细胞特化至关重要，并参与调节女性生殖器官中AR的表达。

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.