Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-2-25
pubmed:abstractText
The response of pituitary gonadotropes to GnRH correlates directly with the concentration of GnRH receptors (GnRHRs) on the cell surface, which is mediated in part at the level of GnRHR gene expression. We have previously localized GnRH responsiveness in the mouse GnRHR (mGnRHR) gene promoter to two elements: activating protein-1 and sequence underlying responsiveness to GnRH-1. This study was designed to investigate potential synergy between GnRH and activin A in transcriptional activation of the mGnRHR gene. In functional transfection studies using alphaT3-1 cells, GnRH agonist stimulation of the mGnRHR gene promoter (-765/+62) resulted in a 10.9-fold increase in activity, which was further increased 2-fold (to 21.3-fold) following activin pretreatment. Activin pretreatment alone had no effect. Deletion of region -387/-308 or mutation of a putative SMAD-binding element at -331/-324 (5'-GTCTAG[T]C-3') abrogated the augmented response to GnRH in the presence of activin but not the response to GnRH alone. Overexpression of SMAD2 and SMAD3 along with SMAD4 increased transcriptional activity of the mGnRHR gene, which was further increased by GnRH agonist stimulation. These data demonstrate that activin augments GnRH-mediated transcriptional activation of the mGnRHR gene and suggest that this effect may be mediated through SMAD transcription factors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
985-97
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Activin A augments GnRH-mediated transcriptional activation of the mouse GnRH receptor gene.
pubmed:affiliation
Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. enorwitz@partners.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't