Effect of activin on production and secretion of prolactin and growth hormone in cultured rat GH3 cells

Tamura, Noboru; Irahara, Minoru; Kuwahara, Akira; Ushigoe, Kenjiro; Sugino, Hiromu; Aono, Toshihiro

doi:10.1530/eje.0.1420506

Cited by 18 publications

(22 citation statements)

References 29 publications

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“…Therefore, TRHinduced follistatin does not have a direct effect on prolactin expression, whereas follistatin affects somatolactotrophs indirectly through inhibition of activin. Previous reports have demonstrated that activin has an inhibitory effect on PRL production [46,47]. In our studies, we also showed that activin decreases PRL promoter activity and this inhibition is rescued in the presence of follistatin (Fig.…”

Section: Effects Of Follistatin On Somatolac-totroph and Gonadotrsupporting

confidence: 84%

Paracrine Control of Gonadotrophs by Somatolactotrophs through TRHinduced Follistatin Production

Kanasaki¹

2011

TONEUROEJ

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There is increasing evidence for the existence of local regulation of hormone secretion among pituitary cells. Hormone-producing pituitary cells may communicate with each other and with folliculostellate cells. Activin is one of the regulators of follicle stimulating hormone (FSH) secretion and gene expression, whereas follistatin negatively regulates FSH production by binding to and bioneutralizing the effects of activin. In prolactin-secreting GH3 cells, hypothalamic thyrotropin-releasing hormone (TRH) has been known to stimulate prolactin synthesis and secretion. Follistatin is produced in GH3 cells and is up-regulated by TRH in an ERK dependent manner. Prolactin mRNA levels in GH3 cells are not affected by increasing the dose of exogenous follistatin, and TRH-induced prolactin expression is not modulated in the presence of follistatin. Follistatin produced in somatolactotroph GH3 cells does not affect prolactin production in these cells. In pituitary gonadotroph cell line, L T2, activin increases FSH promoter activity and mRNA expression, and follistatin completely inhibits this activin-increased FSH gene expression. On the other hand, activin reduces the basal activity of prolactin transcription and follistatin prevents these effects. When GH3 cells and L T2 cells are co-cultured, activin-induced FSH promoter activity is completely inhibited in the presence of follistatin. In addition, FSH mRNA is not detected in L T2 cells, when co-cultured with GH3 cells. These observations using the model for somatolactotroph and gonadotroph suggest the possibility that somatolactotrophs and gonadotrophs interact with each other, and TRH might indirectly affect gonadotropin production though follistatin.

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Section: Effects Of Follistatin On Somatolac-totroph and Gonadotrsupporting

confidence: 84%

Paracrine Control of Gonadotrophs by Somatolactotrophs through TRHinduced Follistatin Production

Kanasaki¹

2011

TONEUROEJ

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“…In our study, whether MEK and p38 MAPK respectively mediated the induction of IL-6 on hGH-gene expression or interacted with each other remains to be determined. Delidow et al (1991) and Tamura et al (2000) found that the regulatory mechanism of GH and PRL-gene transcription by activin and TGF-b was independent of Pit-1 protein in GH3 cells. In this study, we also found that Pit-1 may not be involved in the stimulatory effect of IL-6 on hGHpromoter activity, although a significant number of studies showed that Pit-1 plays a pivotal role in basal and GHRHinduced GH-gene transcription.…”

Section: Discussionmentioning

confidence: 99%

“…These cells have been used previously by ourselves and others as an accepted model for studying both GH-gene expression and the molecular mechanism involved (Tamura et al 2000, Gong et al 2003a, 2003b, Adriao et al 2004.…”

Section: Plasmid Constructsmentioning

confidence: 99%

The regulatory mechanism by which interleukin-6 stimulates GH-gene expression in rat GH3 cells

Gong

Shi

Deng

2006

Journal of Endocrinology

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The present study was performed to elucidate the effect of interleukin (IL)-6 on the human GH (hGH)-gene expression in GH3 rat pituitary tumor cells using stable transfection of the hGH promoter fused to a luciferase reporter gene. Our results showed that IL-6 (10 2 -10 4 U/ml) stimulated GH secretion and synthesis, and promoted the luciferase expression in stably transfected GH3 cells with the maximal action of 1$99 times above the control by 10 4 U/ml IL-6. Among the inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 mM) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 mM) completely blocked the stimulatory effect of IL-6. Western blot analysis demonstrated that IL-6 indeed increased the activation of phosphorylated MEK and p38 MAPK in GH3 cells. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-6 induction of hGH-promoter activity. To identify the DNA sequence that mediated the effect of IL-6, six deletion constructs of hGH promoter were created. The stimulatory effect of IL-6 was abolished following deletion of the K196 to K132 bp fragment. In conclusion, our data show that IL-6 promotes GH secretion and synthesis by rat pituitary GH3 cells. The stimulatory effect of IL-6 on hGH-gene promoter appears to require the activation of MEK and p38 MAPK, and a fragment of promoter sequence that spans the K196 to K132 bp of the gene, but may be unrelated to Pit-1 protein.

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“…GH3 cells, a rat pituitary tumor cell line that secretes both GH and prolactin (PRL), was purchased from American Type Culture Collection (Manassas, Va., USA) and used for the study on GH release and regulation of expression [21, 22]. GH3 cells were maintained in Dulbecco’s modified Eagle’s Medium (Life Technologies, Grand Island, N.Y., USA) supplemented with 20% fetal bovine serum and antibiotics (100 U/ml penicillin and 100 U/ml streptomycin) in a 5% CO 2 -95% air atmosphere at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Stimulatory Effect of Interleukin-1β on Growth Hormone Gene Expression and Growth Hormone Release from Rat GH3 Cells

2005

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Our previous studies demonstrated that interferon gamma increases the human (h) growth hormone (GH) gene promoter activity in rat pituitary GH3 cells, and its regulatory mechanism may be different from the classical GH-releasing hormone-induced regulatory mechanism. Interleukin-1β (IL-1β) is thought to induce the release of GH by pituitary cells, but whether or not and by which mechanisms IL-1β regulates GH synthesis remains unclear. The purpose of our study was thus to investigate the effect of IL-1β on the hGH gene expression in GH3 rat pituitary tumor cells using stable transfection of the hGH promoter fused to a luciferase reporter gene. Our results showed that IL-1β (10–10⁴ U/ml) increased GH secretion and synthesis and that 10² to 10⁴ U/ml IL-1β promoted the luciferase expression in stable GH3 cells, with a maximal action of 1.61 times over that of controls. Among inhibitors of intracellular signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 µM) and p38 MAPK inhibitor SB203580 (5 µM)blocked completely the stimulatory effect of IL-1β, and the phosphoinositide 3-kinase inhibitor LY294002 (10 µM) blocked partially the induction of IL-1β. Western blot analysis demonstrated that IL-1β increased the activation of phosphorylated MEK and p38 MAPK in GH3 cells. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1β induction of hGH promoter activity. To identify the DNA sequence that mediated the effect of IL-1β, six deletion constructs of hGH promoter were created. The stimulatory effect of IL-1β was abolished following deletion of the –196- to –132-bp fragment. In conclusion, our data show that IL-1β promotes GH secretion and synthesis by rat pituitary GH3 cells. The stimulatory effect of IL-1β on the hGH gene promoter appears to require the activation of MEK, p38 MAPK, and phosphoinositide 3-kinase and a fragment of promoter sequence that spans the –196- to –132-bp fragment of the gene, but is unrelated to the Pit-1 protein.

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Effect of activin on production and secretion of prolactin and growth hormone in cultured rat GH3 cells

Cited by 18 publications

References 29 publications

Paracrine Control of Gonadotrophs by Somatolactotrophs through TRHinduced Follistatin Production

Paracrine Control of Gonadotrophs by Somatolactotrophs through TRHinduced Follistatin Production

The regulatory mechanism by which interleukin-6 stimulates GH-gene expression in rat GH3 cells

Stimulatory Effect of Interleukin-1β on Growth Hormone Gene Expression and Growth Hormone Release from Rat GH3 Cells

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