GnRH-regulated expression of Jun and JUN target genes in gonadotropes requires a functional interaction between TCF/LEF family members and beta-catenin.

Molecular Endocrinology
Travis B SalisburyJohn H Nilson

Abstract

GnRH regulates gonadotrope function through a complex transcriptional network that includes three members of the immediate early gene family: Egr1, Jun, and Atf3. These DNA-binding proteins act alone or in pairs to confer hormonal responsiveness to Cga, Lhb, Fshb, and Gnrhr. Herein we suggest that the transcriptional response of Jun requires a functional interaction between the T-cell factor (TCF)/lymphoid enhancer factor (LEF) family of DNA-binding proteins and beta-catenin (officially CTNNB1), a coactivator of TCF/LEF. Supporting data include demonstration that GnRH increases activity of TOPflash, a TCF/LEF-dependent luciferase reporter, in LbetaT2 cells, a gonadotrope-derived cell line. Additional cotransfection experiments indicate that a dominant-negative form of TCF7L2 (TCFDN) that binds DNA, but not beta-catenin, blocks GnRH induction of TOPflash. Overexpression of AXIN, an inhibitor of beta-catenin, also reduces GnRH stimulation of TOPflash. Transduction of LbetaT2 cells with TCFDN adenoviruses diminishes GnRH stimulation of Jun mRNA without altering expression of Egr1 and Atf3, two other immediate early genes that confer GnRH responsiveness. Reduction of beta-catenin in LbetaT2 cells, through stable expression of short...Continue Reading

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Citations

Jul 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sally A Camper
Mar 27, 2012·Molecular Endocrinology·April K BinderJohn H Nilson
Dec 6, 2012·Molecular Endocrinology·Qian WangStuart C Sealfon
Apr 21, 2010·Fertility and Sterility·Daniel J BernardPankaj Lamba
Jul 11, 2012·Journal of Neuroendocrinology·P MelamedL Pnueli
Dec 6, 2018·Endocrinology·George A StamatiadesUrsula B Kaiser
Jun 12, 2013·Molecular Endocrinology·Nathan C LawMary Hunzicker-Dunn
Aug 13, 2009·Molecular Cancer Research : MCR·Anas SaadeddinAbdolrahman Shams Nateri
Dec 23, 2009·Molecular and Cellular Endocrinology·S W DavisS A Camper

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