Lgr4 Controls Specialization of Female Gonads in Mice1

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). Rece...

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Veröffentlicht in:Biology of reproduction 2015-10, Vol.93 (4)
Hauptverfasser: Koizumi, Masae, Oyama, Kazunori, Yamakami, Yukiko, Kida, Tomoyo, Satoh, Ryo, Kato, Shigeki, Hidema, Shizu, Oe, Tomoyuki, Goto, Takaaki, Clevers, Hans, Nawa, Akihiro, Nishimori, Katsuhiko
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Sprache:eng
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Zusammenfassung: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.
ISSN:0006-3363
1529-7268
DOI:10.1095/biolreprod.114.123638