The involvement of phosphatidylinositol 3-kinase in gonadotropin-releasing hormone-induced gonadotropin α- and FSHβ-subunit genes expression in clonal gonadotroph LβT2 cells☆

Mutiara, Sandra; Kanasaki, Haruhiko; Harada, Takashi; Oride, Aki; Miyazaki, Kohji

doi:10.1016/j.mce.2007.12.001

Cited by 17 publications

(13 citation statements)

References 46 publications

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“…In our previous study, we reported that IGF1 stimulation activates MAPK3/1 in LbT2 cells [35]. In this study, we examined whether IGF1 increased DUSP1 protein in a manner similar to GnRH.…”

Section: Effect Of Insulin-like Growth Factor 1 (Igf1) On Dusp1 Exprementioning

confidence: 93%

“…IGF1 signals are transmitted through phosphatidylinositol 3-kinase (PI3-kinase) which triggers the MAPK signaling cascade [54]. Previously, we have demonstrated that MAPK3/1 is phosphorylated by IGF1 similar to that of GnRH [35]. As shown in Figure 8, although this neuropeptide has the ability to stimulate MAPK3/1 phosphorylation, IGF1 fails to stimulate gonadotropin subunit promoter activity.…”

Section: Role Of Dusp1 Expression On Gonadotropin Expressionmentioning

confidence: 99%

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Induction of Dual Specificity Phosphatase 1 (DUSP1) by Gonadotropin-Releasing Hormone (GnRH) and the Role for Gonadotropin Subunit Gene Expression in Mouse Pituitary Gonadotroph LbetaT2 Cells1

Purwana

Kanasaki

Oride

et al. 2010

Biology of Reproduction

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We examined the expression of dual specificity phosphatase 1 (DUSP1) by gonadotropin-releasing hormone (GnRH) stimulation and investigated the role of DUSP1 on gonadotropin gene expression using LbetaT2 gonadotroph cell line. DUSP1 expression was markedly increased 60 min after GnRH stimulation, and mitogen-activated protein kinase 3/1 (MAPK3/1) activation was gradually decreased after 60 min. GnRH-induced MAPK3/1 activation was completely inhibited by U0126, a MEK inhibitor, whereas GnRH-induced DUSP1 expression was partially inhibited by U0126. GnRH-induced DUSP1 induction was inhibited by triptolide, a diterpenoid triepoxide. In contrast, this compound potentiated MAPK3/1 activation. U0126 prevented GnRH-stimulated gonadotropin subunit promoter activation dose dependently, and 10 muM of U0126 reduced the effects of GnRH on the Lhb and Fshb promoters to 79.15% and 55.66%, respectively. GnRH-stimulated activation of Lhb and Fshb promoters as well as serum response factor (Srf) promoters were almost completely inhibited by triptolide, suggesting that this component had a nonspecific effect to the cells. Dusp1 siRNA reduced the expression of DUSP1 and augmented MAPK3/1 phosphorylation, but it did not increase of gonadotropin promoters. By overexpression of DUSP1, both GnRH-stimulated Lhb and Fshb promoters were significantly reduced. We have previously shown that insulin-like growth factor 1 (IGF1) increases MAPK3/1 but does not activate gonadotropin subunit promoters. IGF1 failed to induce DUSP1 expression. In addition, under pulsatile GnRH stimulation, DUSP1 expression was observed following high-frequency GnRH pulses but not following low-frequency pulses. Our study demonstrated that DUSP1, induced by GnRH, functions not only as an MAPK3/1-inactivating phosphatase but also as an important mediator in gonadotropin subunit gene expression regulation.

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“…In our previous study, we reported that IGF1 stimulation activates MAPK3/1 in LbT2 cells [35]. In this study, we examined whether IGF1 increased DUSP1 protein in a manner similar to GnRH.…”

Section: Effect Of Insulin-like Growth Factor 1 (Igf1) On Dusp1 Exprementioning

confidence: 93%

Section: Role Of Dusp1 Expression On Gonadotropin Expressionmentioning

confidence: 99%

Induction of Dual Specificity Phosphatase 1 (DUSP1) by Gonadotropin-Releasing Hormone (GnRH) and the Role for Gonadotropin Subunit Gene Expression in Mouse Pituitary Gonadotroph LbetaT2 Cells1

Purwana

Kanasaki

Oride

et al. 2010

Biology of Reproduction

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“…Several studies have reported that IGF-1 stimulates LH synthesis and /or secretion (Soldani et al 1994, Kanematsu et al 1991, Whitley et al 1995, Soldani et al 1995, Hashizume et al 2002, Xia et al 2001) although one study found that while IGF-1 activated PI3K signaling in LβT2 cells (Mutiara et al 2008), no role was observed for IGF-1R activation in regulating gene expression of Lhb , Fshb or the Cga genes and this signaling pathway may regulate LH secretion (Weiss et al 2003). These effects may not mediate acute changes in IGF-1 levels since one study found no effect of short term IGF-1 treatment on LH synthesis and release (Weiss et al 2006) and noted that effects of IGF-I on LH-secretion in female rat pituitary cells require long-term treatment (Xia et al 2001).…”

Section: Igf-1 Regulation Of Neuroendocrine Functionmentioning

confidence: 99%

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

Wolfe

DiVall

2014

Frontiers in Neuroendocrinology

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The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction.

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“…Changes in GnRH pulse frequency have been shown to differentially regulate gonadotropin subunit gene expression [18]. In the immortalized murine pituitary gonadotroph-derived cell line LbT2, rapid GnRH pulses delivered at 30-min intervals maximally stimulate expression of the Lhb gene, whereas less frequent GnRH pulses at 2-h intervals preferentially stimulate expression of the Fshb gene [19,20]. Various GnRH pulse frequencies have also been shown to affect expression of other gonadotropin genes, including GnRH receptor (GnRHR), follistatin, inhibin, and PACAP receptor (PAC1R) [20][21][22][23][24], although how GnRH pulse frequency determines the specificity of gonadotropin subunit gene expression is unclear.…”

Section: Introductionmentioning

confidence: 99%

Induction of Dual-Specificity Phosphatase 1 (DUSP1) by Pulsatile Gonadotropin-Releasing Hormone Stimulation: Role for Gonadotropin Subunit Expression in Mouse Pituitary LbetaT2 Cells1

Purwana

Kanasaki

Mijiddorj

et al. 2011

Biology of Reproduction

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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.

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The involvement of phosphatidylinositol 3-kinase in gonadotropin-releasing hormone-induced gonadotropin α- and FSHβ-subunit genes expression in clonal gonadotroph LβT2 cells☆

Cited by 17 publications

References 46 publications

Induction of Dual Specificity Phosphatase 1 (DUSP1) by Gonadotropin-Releasing Hormone (GnRH) and the Role for Gonadotropin Subunit Gene Expression in Mouse Pituitary Gonadotroph LbetaT2 Cells1

Induction of Dual Specificity Phosphatase 1 (DUSP1) by Gonadotropin-Releasing Hormone (GnRH) and the Role for Gonadotropin Subunit Gene Expression in Mouse Pituitary Gonadotroph LbetaT2 Cells1

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1)

Induction of Dual-Specificity Phosphatase 1 (DUSP1) by Pulsatile Gonadotropin-Releasing Hormone Stimulation: Role for Gonadotropin Subunit Expression in Mouse Pituitary LbetaT2 Cells1

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