Egr-1 Is a Downstream Effector of GnRH and Synergizes by Direct Interaction with Ptx1 and SF-1 To Enhance Luteinizing Hormone β Gene Transcription

Tremblay, Jacques; Drouin, Jacques

doi:10.1128/mcb.19.4.2567

Cited by 254 publications

(271 citation statements)

References 66 publications

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“…3C), and was in sharp contrast to the synergistic Pitx-1:Egr-1 interaction observed in LH␤-luciferase promoter-reporter experiments (Fig. 3D) and reported previously (20).…”

Section: Resultscontrasting

confidence: 47%

“…In addition, the expression of Egr-1 in gonadotrophs is directly induced by pulsatile stimulation with GnRH and is thought to be a key element in the GnRH-induced stimulation of LH␤ transcription (20,24). We have recently identified putative cis-elements for Pitx-1 and these other gonadotroph-associated transcription factors in the rat MT 1 promoter (25), suggesting that these factors might also interact to regulate melatonin receptor expression in the developing pituitary gland.…”

mentioning

confidence: 99%

“…The development and function of gonadotroph cells is also dependent on lineage-specifying transcription factors, including early growth response factor 1 (Egr-1), steroidogenic factor-1 (SF-1), and GATA binding protein-2 (GATA-2) (18)(19)(20)(21)(22), which enhance the trans-activation of gonadotroph-associated genes, such as LH␤ (14,(18)(19)(20)(21)(22)(23)(24). In addition, the expression of Egr-1 in gonadotrophs is directly induced by pulsatile stimulation with GnRH and is thought to be a key element in the GnRH-induced stimulation of LH␤ transcription (20,24).…”

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confidence: 99%

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Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland

Johnston

Messager

Ebling

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Melatonin is produced nocturnally by the pineal gland and is a neurochemical representation of time. It regulates neuroendocrine target tissues through G-protein-coupled receptors, of which MT1 is the predominant subtype. These receptors are transiently expressed in several fetal and neonatal tissues, suggesting distinct roles for melatonin in development and that specific developmental cues define time windows for melatonin sensitivity. We have investigated MT 1 gene expression in the rat pituitary gland. MT1 mRNA is confined to the pars tuberalis region of the adult pituitary, but in neonates extends into the ventral pars distalis and colocalizes with luteinizing hormone ␤-subunit (LH␤) expression. This accounts for the well documented transient sensitivity of rat gonadotrophs to melatonin in the neonatal period. Analysis of an upstream fragment of the rat MT 1 gene revealed multiple putative response elements for the transcription factor pituitary homeobox-1 (Pitx-1), which is expressed in the anterior pituitary from Rathke's pouch formation. A Pitx-1 expression vector potently stimulated expression of both MT 1-luciferase and LH␤-luciferase reporter constructs in COS-7 cells. Interestingly, transcription factors that synergize with Pitx-1 to trans-activate gonadotroph-associated genes did not potentiate Pitx-1-induced MT 1-luciferase activity. Moreover, the transcription factor, early growth response factor-1, which is induced by gonadotrophinreleasing hormone (GnRH) and trans-activates LH␤ expression, attenuated Pitx-1-induced MT 1-luciferase activity. Finally, pituitary MT 1 gene expression was 4-fold higher in hypogonadal (hpg) mice, which do not synthesize GnRH, than in their wild-type littermates. These data suggest that establishment of a mature hypothalamic GnRH input drives the postnatal decline in pituitary MT 1 gene expression.

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“…3C), and was in sharp contrast to the synergistic Pitx-1:Egr-1 interaction observed in LH␤-luciferase promoter-reporter experiments (Fig. 3D) and reported previously (20).…”

Section: Resultscontrasting

confidence: 47%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland

Johnston

Messager

Ebling

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…To test the role of the putative proximal binding site in the insulin induction of GnRH promoter activity, we generated a mutation of the putative Egr-1 binding site (−67 mutant) previously shown to obliterate Egr-1 binding (Tremblay and Douin, 1999) in the context of the −1250LUC contruct. The wild type and mutant sequences of the proximal putative Egr-1 binding site are shown in Figure 6A.…”

Section: The Putative Egr-1 Binding Site In the Proximal Gnrh Promotementioning

confidence: 99%

“…The gonadotrophs of these mice are atrophic and do not synthesize LH. Egr-1 is involved in GnRH-dependent stimulation of LHβ gene expression as was shown by several laboratories (Tremblay and Douin, 1999;Dorn et al, 1999;Russell et al, 2003;Mouillet et al, 2004). Although GnRH neurons were detected in the Egr-1 knockout mice, the function of these neurons was not examined.…”

Section: Introductionmentioning

confidence: 96%

Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin

DiVall

Radovick

Wolfe

2007

Molecular and Cellular Endocrinology

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SUMMARYInsulin increases gonadotropin-releasing hormone (GnRH) gene expression in in vitro models of GnRH neurons. Early growth response-1 (Egr-1) is a transcription factor that mediates the effect of insulin on target genes. In the GN11 cell line-an immortalized GnRH-secreting neuronal cell line -insulin maximally increases Egr-1 mRNA after 30 minutes of treatment and Egr-1 protein and GnRH mRNA after 60 minutes of treatment. Egr-1 small interfering RNA blocks the insulin-induced increase in GnRH promoter activity, measured as luciferase expression. Chromatin immunoprecipitation using Egr-1 antibody precipitates DNA in a proximal region of the GnRH promoter but not DNA in a distal region. Mutagenesis of a putative Egr-1 binding site within the proximal region blocks the insulin-induced increase in GnRH promoter activity. Thus, Egr-1 binds the GnRH promoter at a site between −67 and −76 bp from the transcriptional start site to mediate the insulin induced increase in GnRH gene transcription.

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P itx ( P tx) Transcription Factors

Drouin

2002

Wiley Encyclopedia of Molecular Medicine

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Egr-1 Is a Downstream Effector of GnRH and Synergizes by Direct Interaction with Ptx1 and SF-1 To Enhance Luteinizing Hormone β Gene Transcription

Cited by 254 publications

References 66 publications

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland

Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland

Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin

P itx ( P tx) Transcription Factors

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