The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter

Molecular Endocrinology
Anne GrangerJean-Noël Laverrière

Abstract

The GnRH receptor (GnRH-R) plays a central role in mammalian reproductive function throughout adulthood. It also appears as an early marker gene of the presumptive gonadotrope lineage in developing pituitary. Here, using transient transfections combined with DNA/protein interaction assays, we have delineated cis-acting elements within the rat GnRH-R gene promoter that represent targets for the LIM-homeodomain (LIM-HD) proteins, Isl-1 and Lhx3. These factors, critical in early pituitary development, are thus also crucial for gonadotrope-specific expression of the GnRH-R gene. In heterologous cells, the expression of Isl-1 and Lhx3, together with steroidogenic factor 1 (SF-1), culminates in the activation of both the rat as well as human GnRH-R promoter, suggesting that this combination is evolutionarily conserved among mammals. The specificity of these LIM-HD factors is attested by the inefficiency of related proteins, including Lhx5 and Lhx9, to activate the GnRH-R gene promoter, as well as by the repressive capacity of a dominant-negative derivative of Lhx3. Accordingly, targeted deletion of the LIM response element decreases promoter activity. In addition, experiments with Gal4-SF-1 fusion proteins suggest that LIM-HD protein...Continue Reading

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Citations

Jan 31, 2009·Journal of Biosciences·Y J JingM Zhao
Oct 20, 2009·Endocrine Reviews·Daniel KelbermanMehul T Dattani
Mar 29, 2013·Journal of Molecular Endocrinology·Muhammad IshaqRaymond Counis
Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Stephanie C ColvinSimon J Rhodes
Jan 11, 2007·Molecular and Cellular Endocrinology·Rachel D MullenSimon J Rhodes
Apr 22, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Geng TianReinald Fundele
Nov 27, 2007·Developmental Biology·Buffy S EllsworthSally A Camper
Sep 10, 2014·Journal of Endocrinological Investigation·F CastinettiT Brue
Jul 13, 2016·Molecular and Cellular Endocrinology·Jean-Noël LaverrièreJoëlle Cohen-Tannoudji
Jul 27, 2011·Nature Reviews. Endocrinology·Kelly L PrinceSimon J Rhodes
Nov 1, 2008·Expert Review of Endocrinology & Metabolism·Frederic CastinettiThierry Brue
Mar 1, 2007·The Journal of Clinical Endocrinology and Metabolism·Roland W PfaeffleSimon J Rhodes
Aug 22, 2015·Molecular Endocrinology·F CastinettiS A Camper
Sep 29, 2018·European Journal of Human Genetics : EJHG·Nicolas JullienFrederic Castinetti

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