Species differences in GnRH activation of the LHβ promoter: role of Egr1 and Sp1

Activation of the luteinizing hormone β (LHβ) promoter by gonadotropin-releasing hormone (GnRH) via the transcription factor early growth response protein-1 (Egr1) has been well characterized. To determine the mechanisms affecting Egr1 regulation of LHβ, we analyzed five different species of LHβ pro...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2002-03, Vol.189 (1), p.85-96
Main Authors: Call, Gerald B, Wolfe, Michael W
Format: Article
Language:English
Subjects:
Early growth response protein 1
Gonadotropin-releasing hormone
Luteinizing hormone β
LβT2
αT3-1
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Summary:Activation of the luteinizing hormone β (LHβ) promoter by gonadotropin-releasing hormone (GnRH) via the transcription factor early growth response protein-1 (Egr1) has been well characterized. To determine the mechanisms affecting Egr1 regulation of LHβ, we analyzed five different species of LHβ promoters (equine, mouse, rat, bovine and human). Electrophoretic mobility shift assays (EMSAs) identified multiple transcription factors binding to the Egr regions on the LHβ promoter. Species-specific differences existed in the binding affinity for Sp1, Sp3, steroidogenic factor-1 (SF-1) and Egr1. Upon mutation of the Egr elements, competition for the binding of all zinc finger proteins was lost, suggesting that the Sp proteins compete for binding to the same site that Egr1 occupies. In addition, the promoters from species that had the highest affinity for Sp1 also had the lowest activation by Egr1 and GnRH. Thus we hypothesize that Sp1 competes for Egr1 binding to the Egr elements on the LHβ promoter and thus inhibits the ability of GnRH and Egr1 to activate the LHβ promoter.
ISSN:0303-7207
1872-8057
DOI:10.1016/S0303-7207(01)00744-4