Lgr4 Controls Specialization of Female Gonads in Mice

被引：21

作者：

Koizumi, Masae ^{[1
,3
]}

Oyama, Kazunori ^{[1
]}

Yamakami, Yukiko ^{[1
]}

Kida, Tomoyo ^{[1
]}

Satoh, Ryo ^{[2
]}

Kato, Shigeki ^{[1
]}

Hidema, Shizu ^{[1
]}

Oe, Tomoyuki ^{[2
]}

Goto, Takaaki ^{[2
]}

Clevers, Hans ^{[4
]}

Nawa, Akihiro ^{[3
]}

Nishimori, Katsuhiko ^{[1
]}

机构：

[1] Tohoku Univ, Mol Biol Lab, Grad Sch Agr Sci, Sendai, Miyagi 9818555, Japan

[2] Tohoku Univ, Dept Bioanalyt Chem, Grad Sch Pharmaceut Sci, Sendai, Miyagi 9818555, Japan

[3] Ehime Univ, Dept Obstet & Gynecol, Sch Med, Toon, Japan

[4] Univ Med Ctr Utrecht, Hubrecht Inst, Royal Netherlands Acad Arts & Sci, Utrecht, Netherlands

来源：

BIOLOGY OF REPRODUCTION | 2015年 / 93卷 / 04期

基金：

日本学术振兴会;

关键词：

female reproductive tract; sex differentiation; steroid hormones/steroid hormone receptor; testosterone; TRANSCRIPTION FACTOR FOXL2; PROTEIN-COUPLED RECEPTORS; SEX DETERMINATION; SIGNALING PATHWAY; WNT/BETA-CATENIN; HORMONE RECEPTOR; DIFFERENTIATION; OVARY; R-SPONDIN1; LIGANDS;

D O I：

10.1095/biolreprod.114.123638

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

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