Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.25 (MEKK1)
 1,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Follistatin regulates FSHbeta gene expression by binding to and bioneutralizing activin effects. In this study, we found that thyrotropin-releasing hormone (TRH) increased follistatin gene expression in pituitary somatolactotroph GH3 cells. Treatment of GH3 with 100 nM TRH significantly increased follistatin mRNA expression as determined by real time PCR. TRH-induced follistatin expression was significantly abrogated in the presence of MEK inhibitor, U0126. Overexpression of constitutive active MEKK in GH3 cells dramatically increased follistatin expressions. Transfection of GH3 cells with follistatin siRNA reduced endogenous follistatin mRNA expression, but failed to modulate prolactin promoter activity. Prolactin mRNA levels were not affected by increasing the dose of follistatin, and TRH-induced prolactin promoter activity was not modulated in the presence of follistatin. In other experiments using pituitary gonadotroph LbetaT2 cells, activin increased FSHbeta promoter activity and mRNA expression, and follistatin completely inhibited this activin-increased FSHbeta gene expression. Treatment of GH3 cells with activin reduced the basal activity of prolactin promoter and follistatin prevented this effect. GH3 cells were co-cultured with LbetaT2 cells, which had been transfected with FSHbeta promoter-linked luciferase vectors and treated with activin in the presence of TRH. Activin-induced FSHbeta promoter activity was completely inhibited in the presence of TRH. In addition to that, FSHbeta mRNA was not detected from LbetaT2 cells which were co-cultured with GH3 cells. Our current results suggest the possibility that TRH increases follistatin gene expression in prolactin-producing cells in association with ERK pathways. Somatolactotroph-derived follistatin affects gonadotrophs by countering activin-induced FSHbeta gene expression in a paracrine fashion.
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PMID:Follistatin, induced by thyrotropin-releasing hormone (TRH), plays no role in prolactin expression but affects gonadotropin FSHbeta expression as a paracrine factor in pituitary somatolactotroph GH3 cells. 1944 81

The purpose of the present study was to examine the signal transduction pathways involved in follistatin gene expression induced by GnRH in the LbetaT2 cell line. The LHbeta-subunit was predominantly increased by high frequency GnRH pulses (30 min interval); whereas low frequency pulses (120 min) increased FSHbeta. In a static culture, follistatin expression was significantly increased at 12 h (2.35 +/- 0.80-fold) after the addition of GnRH. Following pulsatile stimulation, follistatin mRNA was increased by high frequency GnRH pulses, but not by low frequency pulses. In a static culture, GnRH maximally activated extracellular signal-regulated kinase (ERK) 10 min (3.2 +/- 0.55-fold) after treatment. In addition, intracellular cAMP accumulated up to 2.1 +/- 0.76-fold. Follistatin promoter activity was significantly increased following transfection with either a constitutively active cAMP dependent protein kinase (PKA) or a constitutively active MEK kinase (MEKK). The induction of follistatin gene expression by GnRH was completely inhibited by H89, a protein kinase A inhibitor, and U0126, a MEK inhibitor. Follistatin gene expression was also activated by both PACAP and CPT-cAMP under static culture conditions. Maximal ERK activation levels were nearly identical regardless of GnRH pulse frequency; however, high frequency GnRH pulses elevated both the intracellular cAMP level as well as cAMP-response element (Cre) promoter activity. These results suggest that both the PKA and ERK pathways are necessary for the induction of the follistatin promoter. Furthermore, the intracellular cAMP level, but not ERK activity, determined whether follistatin was induced following high frequency GnRH pulses.
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PMID:Follistatin gene expression by gonadotropin-releasing hormone: a role for cyclic AMP and mitogen-activated protein kinase signaling pathways in clonal gonadotroph LbetaT2 cells. 1953 41