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1 January 2004 Differential Activation of the Luteinizing Hormone β-Subunit Promoter by Activin and Gonadotropin-Releasing Hormone: A Role for the Mitogen-Activated Protein Kinase Signaling Pathway in LβT2 Gonadotrophs
Yoko Yamada, Hideyuki Yamamoto, Toshie Yonehara, Haruhiko Kanasaki, Hiroyuki Nakanishi, Eishichi Miyamoto, Kohji Miyazaki
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Abstract

LH consists of α- and β-subunits, and synthesis of the β-subunit has been reported to be the rate-limiting step in LH production. In this study, we found that activin A increased both the LHβ mRNA level and LH content in cells of the gonadotroph cell line, LβT2. We next examined the effects of activin A and GnRH on LHβ promoter activity by reporter gene assay and compared the signal transduction pathways. Activin A and GnRH activated the LHβ promoter, and the response to a combination of activin A and GnRH was higher than that to activin A or GnRH alone. The effects of activin A and GnRH were specifically inhibited by inhibin-like peptide and antide, a GnRH antagonist, respectively. The activation of the LHβ promoter by GnRH was inhibited by PD098059 and U0126, MAP kinase kinase (MEK) inhibitors. In contrast, these protein kinase inhibitors did not inhibit the activin A-induced activation. GnRH, but not activin A, activated MAP kinase in LβT2 cells. Overexpression of constitutively active MEK1 or MEK kinase activated both MAP kinase and the LHβ promoter. Furthermore, GnRH, but not activin A, strongly induced SRE-mediated transcription, a known target of the MAP kinase pathway. These results suggest that GnRH activates the LHβ promoter via the MAP kinase pathway and that activin A-induced activation of the LHβ promoter is independent of the MAP kinase pathway.

Yoko Yamada, Hideyuki Yamamoto, Toshie Yonehara, Haruhiko Kanasaki, Hiroyuki Nakanishi, Eishichi Miyamoto, and Kohji Miyazaki "Differential Activation of the Luteinizing Hormone β-Subunit Promoter by Activin and Gonadotropin-Releasing Hormone: A Role for the Mitogen-Activated Protein Kinase Signaling Pathway in LβT2 Gonadotrophs," Biology of Reproduction 70(1), 236-243, (1 January 2004). https://doi.org/10.1095/biolreprod.103.019588
Received: 20 May 2003; Accepted: 1 September 2003; Published: 1 January 2004
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KEYWORDS
activin
anterior pituitary
gonadotropin-releasing hormone
kinases
luteinizing hormone
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