Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-4-16
pubmed:abstractText
GnRH regulates gonadotrope cells through GnRH receptor activation of the PKC-, MAPK-, and calcium-activated signaling cascades. Due to the paucity of homologous model systems expressing FSHbeta, little is known about the specific mechanisms involved in transcriptional regulation of this gene by GnRH. Previous studies from our laboratory demonstrated that the gonadotrope-derived LbetaT2 cell line expresses FSHbeta mRNA. In the present study we characterized the mechanisms involved in GnRH regulation of the FSHbeta promoter using this cell model. Using transfection assays, we show that GnRH regulation of the ovine FSHbeta promoter involves at least two elements, present between -4152/-2878 and -2550/-1089 bp, in association with one or several elements within the proximal region of the promoter. Surprisingly, the two activating protein-1 sites previously shown to be involved in the FSHbeta response to GnRH in heterologous cells do not play a role in GnRH responsiveness in the gonadotrope cell model. Here we demonstrate that calcium influx itself is not sufficient to confer the response, but it is necessary for both 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and GnRH induction of the FSHbeta gene. Moreover, we show that GnRH regulation of FSHbeta gene expression is mediated by PKC and establish the presence of multiple PKC isozymes in LbetaT2 cells. Interestingly, GnRH and TPA induce activity of the FSHbeta promoter through different, although possibly overlapping, pools of PKC isoforms. This is further supported by the use of a MAPK inhibitor, which abolishes the induction of FSHbeta by GnRH, but not by TPA. In conclusion, we have demonstrated that calcium, PKC, and MAPK signaling systems are all involved in the induction of FSHbeta gene expression by GnRH in the LbetaT2 mouse gonadotrope cell model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1651-9
pubmed:dateRevised
2010-9-20
pubmed:meshHeading
pubmed-meshheading:11956146-Animals, pubmed-meshheading:11956146-Binding Sites, pubmed-meshheading:11956146-Calcium, pubmed-meshheading:11956146-Cells, Cultured, pubmed-meshheading:11956146-Enzyme Activation, pubmed-meshheading:11956146-Enzyme Inhibitors, pubmed-meshheading:11956146-Female, pubmed-meshheading:11956146-Follicle Stimulating Hormone, pubmed-meshheading:11956146-Follicle Stimulating Hormone, beta Subunit, pubmed-meshheading:11956146-Gene Expression Regulation, pubmed-meshheading:11956146-Gonadotropin-Releasing Hormone, pubmed-meshheading:11956146-Isoenzymes, pubmed-meshheading:11956146-Mitogen-Activated Protein Kinases, pubmed-meshheading:11956146-Plasmids, pubmed-meshheading:11956146-Protein Kinase C, pubmed-meshheading:11956146-Response Elements, pubmed-meshheading:11956146-Sheep, pubmed-meshheading:11956146-Signal Transduction, pubmed-meshheading:11956146-Stimulation, Chemical, pubmed-meshheading:11956146-Tetradecanoylphorbol Acetate, pubmed-meshheading:11956146-Transcription Factor AP-1, pubmed-meshheading:11956146-Transcriptional Activation, pubmed-meshheading:11956146-Transfection
pubmed:year
2002
pubmed:articleTitle
Transcriptional activation of the ovine follicle-stimulating hormone-beta gene by gonadotropin-releasing hormone involves multiple signal transduction pathways.
pubmed:affiliation
Department of Reproductive Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0674, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't