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

富含亮氨酸重复序列的G蛋白偶联受体4（Leucine-rich repeat-containing G-protein coupled receptor 4，LGR 4）是一种具有七次跨膜结构的膜受体，我们观察到LGR 4-/-雌性小鼠的卵巢中出现了类似雄性的体细胞，即Wolff管发育异常。Lgr 4-/-雌性小鼠表现出与RSPO 1-、β-连环蛋白-和Wnt 4-缺陷小鼠相似的雄性化。在Lgr 4-/-卵巢体细胞中，Wnt-β连环蛋白信号传导的靶基因Lefl和Axin 2表达降低。另一方面，雄激素受体（AR）表达的Wolffian管和卵巢体细胞的Lgr 4-/-女性增加。本研究提示Lgr 4通过RSPOs和Wnt信号通路的协同作用对卵巢体细胞的特化起关键作用，并参与调节雌性生殖器官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.