Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-4-14
pubmed:abstractText
The regulation of LH and FSH subunit gene expression is under the control of GnRH. Physiological changes in the frequency of pulsatile GnRH release from the hypothalamus result in differential stimulation of alpha-, LHbeta-, and FSHbeta-gene expression. Previous studies indicate that the GnRH receptor couples to G proteins of the G(q/11) family, with phosphoinositide turnover and its resultant increase in intracellular calcium concentration and protein kinase C (PKC) activation, to stimulate secretion of LH and FSH. However, the molecular mechanisms by which GnRH mediates its transcriptional effects remain largely unknown. We used GH3 cells, constitutively expressing the rat GnRH receptor (GGH(3)-1' cells) and transiently transfected with a luciferase reporter gene controlled by either the alpha, LHbeta, or FSHbeta gene regulatory region (alphaLUC, LHbetaLUC, and FSHbetaLUC, respectively), to examine the roles of several signal transduction pathways in the GnRH-mediated stimulation of gonadotropin subunit gene expression. Activation of PKC by phorbol, 12-myristate, 13-acetate resulted in an increase in the luciferase activity of all three gonadotropin subunit gene reporter constructs. Phorbol, 12-myristate, 13-acetate had a greater stimulatory effect, relative to the maximal stimulation with GnRH, for the beta-subunit genes than for the alpha-subunit gene. Depletion of PKC, or inhibition of PKC by GF109203X, demonstrated that PKC-dependent pathways play a larger role in the GnRH-mediated transcriptional control of the LHbeta- and FSHbeta-genes than the alpha-subunit gene. In contrast, an L-type calcium channel agonist, Bay K 8644, was able to stimulate alphaLUC but not LHbetaLUC or FSHbetaLUC. Nimodipine, an L-type calcium channel antagonist, had a larger inhibitory effect on the GnRH response of alphaLUC, relative to LHbetaLUC or FSHbetaLUC. We conclude from these results that the differential regulation of gonadotropin subunit gene expression by GnRH is caused, in part, by differential use of signal transduction pathways, activated upon GnRH binding.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine..., http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers, http://linkedlifedata.com/resource/pubmed/chemical/Follicle Stimulating Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Follicle Stimulating Hormone, beta..., http://linkedlifedata.com/resource/pubmed/chemical/Glycoprotein Hormones, alpha Subunit, http://linkedlifedata.com/resource/pubmed/chemical/Gonadotropin-Releasing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Luteinizing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
139
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1835-43
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9528969-8-Bromo Cyclic Adenosine Monophosphate, pubmed-meshheading:9528969-Animals, pubmed-meshheading:9528969-Calcium, pubmed-meshheading:9528969-Calcium Channel Agonists, pubmed-meshheading:9528969-Calcium Channel Blockers, pubmed-meshheading:9528969-Cell Line, pubmed-meshheading:9528969-Enzyme Activation, pubmed-meshheading:9528969-Follicle Stimulating Hormone, pubmed-meshheading:9528969-Follicle Stimulating Hormone, beta Subunit, pubmed-meshheading:9528969-Gene Expression Regulation, pubmed-meshheading:9528969-Glycoprotein Hormones, alpha Subunit, pubmed-meshheading:9528969-Gonadotropin-Releasing Hormone, pubmed-meshheading:9528969-Luteinizing Hormone, pubmed-meshheading:9528969-Pituitary Gland, Anterior, pubmed-meshheading:9528969-Protein Kinase C, pubmed-meshheading:9528969-Rats, pubmed-meshheading:9528969-Recombinant Fusion Proteins, pubmed-meshheading:9528969-Signal Transduction, pubmed-meshheading:9528969-Tetradecanoylphorbol Acetate, pubmed-meshheading:9528969-Transfection
pubmed:year
1998
pubmed:articleTitle
Differential use of signal transduction pathways in the gonadotropin-releasing hormone-mediated regulation of gonadotropin subunit gene expression.
pubmed:affiliation
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't