Please use this identifier to cite or link to this item: https://doi.org/10.1210/en.2006-0022
Title: Gonadotropin-releasing hormone activation of C-jun, but not early growth response factor-1, stimulates transcription of a luteinizing hormone β-subunit gene
Authors: Melamed, P. 
Zhu, Y.
Siew, H.T.
Xie, M.
Koh, M.
Issue Date: 2006
Citation: Melamed, P., Zhu, Y., Siew, H.T., Xie, M., Koh, M. (2006). Gonadotropin-releasing hormone activation of C-jun, but not early growth response factor-1, stimulates transcription of a luteinizing hormone β-subunit gene. Endocrinology 147 (7) : 3598-3605. ScholarBank@NUS Repository. https://doi.org/10.1210/en.2006-0022
Abstract: Transcription of mammalian LH β-subunit genes (LHβ) is regulated by GnRH through activation of early growth response factor-1 (Egr-1), which interacts synergistically with steroidogenic factor-1 (Sf-1) and pituitary homeobox-1 (Pitx1) at the promoter; Egr-1 is thought to comprise the major mediator of this effect. However, the proximal promoters of LHβ genes in lower vertebrates lack an Egr-1 response element yet are responsive to GnRH; we demonstrate here that the promoter of the Chinook salmon LHβ (csLHβ) gene is also unresponsive to Egr-1. The homologous LHβ promoters in other fish contain a conserved estrogen response element-like sequence, which we recently demonstrated is not required for estrogen receptor (ER) α association with the csLHβ gene. Here we show that the estrogen response element-like element is required for the GnRH effect and for a response to c-jun overexpression. Using plasmid immunoprecipitation, we show that after GnRH exposure, c-jun associates with the intact csLHβ gene promoter through this element. We further show that the effect of c-jun requires its DNA-binding domain and that c-jun interacts with Sf-1 and ERα and exerts synergistic effects on promoter activity with Sf-1, ERα, and Pitx1. Finally, we demonstrate the role of c-jun in mediating the GnRH effect on this gene through knockdown of c-jun expression or use of a dominant negative. We conclude that c-jun mediation of the GnRH effect on the LHβ gene may be common in lower vertebrates and may have preceded an evolutionary divergence in the cis-regulatory elements that led to its function being replaced in mammals by Egr-1. Copyright © 2006 by The Endocrine Society.
Source Title: Endocrinology
URI: http://scholarbank.nus.edu.sg/handle/10635/100785
ISSN: 00137227
DOI: 10.1210/en.2006-0022
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