title: Induction of dual-specificity phosphatase 1 (DUSP1) by pulsatile gonadotropin-releasing hormone stimulation: role for gonadotropin subunit expression in mouse pituitary LbetaT2 cells.
abstract: In pituitary gonadotrophs, GnRH induces expression of the mitogen-activated protein kinases (MAPK3/1) dephosphorylating enzyme, dual-specificity phosphatase 1 (DUSP1). Here we examined DUSP1 expression levels following pulsatile GnRH stimulation of the LbetaT2 gonadotroph cells. DUSP1 expression was increased more prominently following high-frequency (every 30 min) GnRH pulse stimulation (7.02- ± 1.47-fold) than low-frequency (every 120 min) GnRH pulses (2.68- ± 0.09-fold). With high-frequency GnRH pulses, DUSP1 expression increased by 2.89- ± 0.32-fold 2 h after GnRH pulse initiation (four 5-min pulses). DUSP1 expression was not induced following lower frequency GnRH pulses, even when the GnRH concentration was increased. Under high-frequency conditions, MAPK3/1 phosphorylation was observed 10 min after the GnRH pulse and decreased to basal levels after 25 min. However, MAPK3/1 dephosphorylation did not occur concurrently with DUSP1 expression. Overexpression of MAP3K1, a kinase upstream of MAPK3/1, increased both the Lhb and the Fshb subunit promoter activities, which could be completely inhibited by cotransfection with DUSP1-expressing vectors. Serum response factor (Srf) promoter activities induced by MAP3K1 were also prevented by DUSP1 overexpression, confirming that MAPK3/1 has an important role in gonadotropin subunit gene expression. Both high- and low-frequency GnRH pulse stimulation failed to increase the Lhb and Fshb subunit gonadotropin gene expression levels upon DUSP1 overexpression. Our study demonstrates that DUSP1 is specifically expressed following high-frequency GnRH pulses and that this effect may participate in the differential regulation of gonadotropin subunit expression in association with MAPK3/1 phosphorylation.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Indri N
authors.initials: IN
authors.lastname: Purwana
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kanasaki
authors.forename: Tselmeg
authors.initials: T
authors.lastname: Mijiddorj
authors.forename: Aki
authors.initials: A
authors.lastname: Oride
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D002460:Cell Line; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis*; D004790:Enzyme Induction; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics / Q000378:metabolism*; D048728:MAP Kinase Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009994:Osmolar Concentration; D010507:Periodicity; D010766:Phosphorylation; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D026362:Serum Response Factor; D007987:Gonadotropin-Releasing Hormone; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048728:MAP Kinase Kinase Kinase 1; C482578:Map3k1 protein, mouse; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse