Gonadotropin-inhibitory hormone inhibits gnrh-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 Cells

You Lee Son, Takayoshi Ubuka, Robert P. Millar, Haruhiko Kanasaki, Kazuyoshi Tsutsui

    研究成果: Article

    75 引用 (Scopus)

    抄録

    A neuropeptide that directly inhibits gonadotropin secretion from the pituitary was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The presence and functional roles of GnIH orthologs, RF-amide-related peptides (RFRP), that possess a common C-terminal LPXRF-amide (X = LorQ) motif have also been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is an important hypothalamic neuropeptide controlling reproduction, but the detailed signaling pathway mediating the inhibitory effect of GnIH on target cells is still unknown. In the present study, we investigated the pathway of GnIH cell signaling and its possible interaction with GnRH signaling using a mouse gonadotropecell line, LβT2. First, we demonstrated the expression of GnIH receptor mRNA in LβT2 cells by RT-PCR. We then examined the inhibitory effects of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that mRFRP function as an inhibitor of adenylate cyclase. We further showed that mRFRP inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by the inhibition of the protein kinase A pathway. Finally, we demonstrated that mRFRP inhibited GnRHstimulated gonadotropin subunit gene transcriptions and also LH release. Taken together, the results indicate that mRFRP function as GnIH to inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LβT2 cells.

    元の言語English
    ページ(範囲)2332-2343
    ページ数12
    ジャーナルEndocrinology
    153
    発行部数5
    DOI
    出版物ステータスPublished - 2012 5

    Fingerprint

    MAP Kinase Signaling System
    Gonadotropins
    Hormones
    Gonadotropin-Releasing Hormone
    Genes
    Cyclic AMP-Dependent Protein Kinases
    Amides
    Neuropeptides
    Pituitary Gonadotropins
    Peptides
    Quail
    Adenylyl Cyclases
    Hypothalamus
    Reproduction
    Mammals
    Phosphorylation

    ASJC Scopus subject areas

    • Endocrinology

    これを引用

    Gonadotropin-inhibitory hormone inhibits gnrh-induced gonadotropin subunit gene transcriptions by inhibiting AC/cAMP/PKA-dependent ERK pathway in LβT2 Cells. / Son, You Lee; Ubuka, Takayoshi; Millar, Robert P.; Kanasaki, Haruhiko; Tsutsui, Kazuyoshi.

    :: Endocrinology, 巻 153, 番号 5, 05.2012, p. 2332-2343.

    研究成果: Article

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    abstract = "A neuropeptide that directly inhibits gonadotropin secretion from the pituitary was discovered in quail and named gonadotropin-inhibitory hormone (GnIH). The presence and functional roles of GnIH orthologs, RF-amide-related peptides (RFRP), that possess a common C-terminal LPXRF-amide (X = LorQ) motif have also been demonstrated in mammals. GnIH orthologs inhibit gonadotropin synthesis and release by acting on pituitary gonadotropes and GnRH neurons in the hypothalamus via its receptor (GnIH receptor). It is becoming increasingly clear that GnIH is an important hypothalamic neuropeptide controlling reproduction, but the detailed signaling pathway mediating the inhibitory effect of GnIH on target cells is still unknown. In the present study, we investigated the pathway of GnIH cell signaling and its possible interaction with GnRH signaling using a mouse gonadotropecell line, LβT2. First, we demonstrated the expression of GnIH receptor mRNA in LβT2 cells by RT-PCR. We then examined the inhibitory effects of mouse GnIH orthologs [mouse RFRP (mRFRP)] on GnRH-induced cell signaling events. We showed that mRFRP effectively inhibited GnRH-induced cAMP signaling by using a cAMP-sensitive reporter system and measuring cAMP levels, indicating that mRFRP function as an inhibitor of adenylate cyclase. We further showed that mRFRP inhibited GnRH-stimulated ERK phosphorylation, and this effect was mediated by the inhibition of the protein kinase A pathway. Finally, we demonstrated that mRFRP inhibited GnRHstimulated gonadotropin subunit gene transcriptions and also LH release. Taken together, the results indicate that mRFRP function as GnIH to inhibit GnRH-induced gonadotropin subunit gene transcriptions by inhibiting adenylate cyclase/cAMP/protein kinase A-dependent ERK activation in LβT2 cells.",
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    AU - Son, You Lee

    AU - Ubuka, Takayoshi

    AU - Millar, Robert P.

    AU - Kanasaki, Haruhiko

    AU - Tsutsui, Kazuyoshi

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