Lgr4 Controls Specialization of Female Gonads in Mice
Lgr4 Controls Specialization of Female Gonads in Mice
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DOI：
10.1095/biolreprod.114.123638
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发表时间：
2015-10-01
影响因子：
3.6
通讯作者：
Nishimori, Katsuhiko
中科院分区：
文献类型：
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作者：
Koizumi, Masae;Oyama, Kazunori;Nishimori, Katsuhiko
富含亮氨酸重复序列的G蛋白偶联受体4(LGR4)是一种具有七跨膜结构的膜受体。LGR4与促性腺激素受体同源，如卵泡刺激素受体(FSHR)和促黄体生成素/绒毛膜促性腺激素受体(LhcGR)。最近有报道称，LGR4是R-响应蛋白配体的膜受体，介导Wnt/β-catenin信号转导。R-Respondin同源基因(Rsp1)和无翅型MMTV整合位点家族成员4(WNT4)的缺陷导致女性性腺男性化。我们观察到LGR4(-/-)雌性小鼠表现出与雄性性腺相似的沃尔夫管和体细胞的异常发育。LGR4(-/-)雌性小鼠表现出与Rspo1基因缺陷小鼠相似的阳性化。在LGR4(-/-)卵巢体细胞中，作为Wnt/β-catenin信号转导靶基因的淋巴增强因子1(Lef1)和Axin2(Axin2)的表达水平低于野生型小鼠。本研究表明，LGR4通过Rspo1和Wnt/β-catenin的协同信号对卵巢体细胞的特化起关键作用。
Leucine-rich repeat-containing G protein-coupled receptor 4 (Lgr4) is a type of membrane receptor with a seven-transmembrane structure. LGR4 is homologous to gonadotropin receptors, such as follicle-stimulating hormone receptor (Fshr) and luteinizing hormone/choriogonadotropin receptor (Lhcgr). Recently, it has been reported that Lgr4 is a membrane receptor for R-spondin ligands, which mediate Wnt/beta-catenin signaling. Defects of R-spondin homolog (Rspo1) and wingless-type MMTV integration site family, member 4 (Wnt4) cause masculinization of female gonads. We observed that Lgr4(-/-) female mice show abnormal development of the Wolffian ducts and somatic cells similar to that in the male gonads. Lgr4(-/-) female mice exhibited masculinization similar to that observed in Rspo1-deficient mice. In Lgr4(-/-) ovarian somatic cells, the expression levels of lymphoid enhancer-binding factor 1 (Lefl) and Axin2 (Axin2), which are target genes of Wnt/beta-catenin signaling, were lower than they were in wild-type mice. This study suggests that Lgr4 is critical for ovarian somatic cell specialization via the cooperative signaling of Rspo1 and Wnt/beta-catenin.