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.
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2 September 2015
Lgr4 Controls Specialization of Female Gonads in Mice
Masae Koizumi,
Kazunori Oyama,
Yukiko Yamakami,
Tomoyo Kida,
Ryo Satoh,
Shigeki Kato,
Shizu Hidema,
Tomoyuki Oe,
Takaaki Goto,
Hans Clevers,
Akihiro Nawa,
Katsuhiko Nishimori
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Biology of Reproduction
Vol. 93 • No. 4
October 2015
Vol. 93 • No. 4
October 2015
female reproductive tract
sex differentiation
steroid hormones/steroid hormone receptor
testosterone