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2 September 2015 Lgr4 Controls Specialization of Female Gonads in Mice
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Abstract

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.

Masae Koizumi, Kazunori Oyama, Yukiko Yamakami, Tomoyo Kida, Ryo Satoh, Shigeki Kato, Shizu Hidema, Tomoyuki Oe, Takaaki Goto, Hans Clevers, Akihiro Nawa, and Katsuhiko Nishimori "Lgr4 Controls Specialization of Female Gonads in Mice," Biology of Reproduction 93(4), (2 September 2015). https://doi.org/10.1095/biolreprod.114.123638
Received: 27 July 2014; Accepted: 1 August 2015; Published: 2 September 2015
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