Submitted May 20, 2003
Returned for revision June 4, 2003
Accepted September 9, 2003
Pitutitary
Differential Activation of the Luteinizing Hormone
-Subunit Promoter by Activin and
Gonadotropin-Releasing Hormone: A Role for the
Mitogen-Activated Protein Kinase Signaling Pathway in
LT2 Gonadotrophs
Yoko Yamada ,
Hideyuki Yamamoto *,
Toshie Yonehara ,
Haruhiko Kanasaki ,
Hiroyuki Nakanishi ,
Eishichi Miyamoto ,
and
Kohji Miyazaki
* To whom correspondence should be addressed. E-mail: hideyuki{at}gpo.kumamoto-u.ac.jp.
Abstract
LH consists of 
- and 
subunits, and
synthesis of the -subunit has been reported to be
the rate-limiting step in LH production. In this study, we
found that activin A increased both the LH mRNA
level and LH content in cells of the gonadotrophic
line, LT2. We next examined the effects of activin
A and GnRH on LH promoter activity by reporter gene
assay, and compared the signal transduction pathways.
Activin A and GnRH activated the LH 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 LH 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 LT2 cells. Overexpression of constitutively
active MEK1 or MEK kinase activated both MAP kinase and
the LH 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 LH promoter via the MAP
kinase pathway and that activin A-induced activation of
the LH promoter is independent of the MAP kinase
pathway.
Key words:
Activin •
Anterior pituitary •
Gonadotropin-releasing hormone •
Kinases •
Luteinizing hormone
