In vivo Activation of the Interleukin-6 Receptor/gp130 Signaling Pathway in Pituitary Corticotropes of Lipopolysaccharide-Treated Rats

Gautron, Laurent; Lafon, Pierrette; Tramu, G.; Layé, Sophie

doi:10.1159/000068336

Cited by 20 publications

(18 citation statements)

References 43 publications

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“…A few studies demonstrate that IL-6 is an afferent signal to the HPAA during local inflammation (Bethin et al 2000, Turnbull et al 2003, and IL-6 regulates this axis by directly targeting rat pituitary corticotropes, such as stimulating POMC transcription and ACTH release (Bethin et al 2000, Gautron et al 2003. Meanwhile, Bethin et al (2000) found that IL-6R is present on pituitary corticotropes and adrenocortical cells.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, Bethin et al (2000) found that IL-6R is present on pituitary corticotropes and adrenocortical cells. In 2003, Gautron et al (2003) reported for the first time using dual in situ hybridization that corticotropes in the rat pituitary co-express both IL-6R and IL-6R subunit gp130, thus making these cells prone to respond to IL-6. In our present study, we found that IL-6R was also expressed in rat pituitary GH3 cells using RT-PCR analysis.…”

Section: Discussionmentioning

confidence: 99%

“…It has a great influence on many functions, including differentiation, stimulation, and activation of immune cells, or other cells of neuroendocrine origin. Recently, it has also been shown to affect hormone secretion, acting at different levels of HPAA (Arzt 2001, Gautron et al 2003. A considerable number of studies report that IL-6 receptors (IL-6R) are expressed in rodent and human pituitary cells (Shimon et al 1997, Bethin et al 2000, Hanisch et al 2000.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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 importance of these cytokines as modulators of neuroendocrine functions has been recognized, in particular for their actions on the hypothalamic-pituitary-adrenal axis and regulation of the GH secretion [3, 4]. A number of studies demonstrated that IL-2, IL-6, IL-11, and ciliary neurotropic factor (CNTF) stimulate GH secretion by the pituitary gland [5,6,7,8].…”

Section: Introductionmentioning

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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“…In addition, the IL-1 receptor type1 (IL-1R1) has been detected in cells from the anterior lobe of the pituitary gland [6,7], mainly in GHsecreting cells and, to a lesser extent, in PRL and ACTH-secreting cells [8]. The receptors for IL-6 have also been detected in normal pituitary cells, specifically in GH, FSH-LH, PRL and ACTH-secreting cells [4,9,10].…”

Section: Interleukin Expression and Function In Normal And Tumoral Admentioning

confidence: 99%

Prenatal expression of interleukin 1β and interleukin 6 in the rat pituitary gland

et al. 2008

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a b s t r a c tIt is known that interleukin 1b (IL-1b) and interleukin 6 (IL-6) are expressed post-natally in normal and tumoral cells in the anterior pituitary, and that they play a role in both the liberation of different hormones and in the growth, proliferation and tumor formation of the pituitary gland. However, their expression and role during embryonic and fetal development remain unknown. We have performed an immunocytochemistry study of prenatal expression and distribution of IL-1b and IL-6 in isolated embryonic rat Rathke's pouch prior to birth, more specifically between 13.5 and 19.5 days p.c. Western-blot analysis carried out on 19.5-day p.c. embryos showed positive immunolabelling for IL-1b and IL-6. These interleukins were initially expressed simultaneously in the rostral and ventral portions of Rathke's pouch in 15.5-day p.c. embryos, and this expression progressed caudodorsally in later developmental stages, extending to most of the hypophysis before birth. The number of cells expressing these interleukins increased throughout this period: 48.22% of anterior pituitary cells expressed IL-6 in 19.5-day embryos, whilst IL-1b was positive in 39.8% of the cells. Moreover, we have demonstrated that some adenohypophyseal cells co-express both interleukins. Such findings represent the first step towards an understanding of the physiological role of these interleukins in anterior pituitary development.

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In vivo Activation of the Interleukin-6 Receptor/gp130 Signaling Pathway in Pituitary Corticotropes of Lipopolysaccharide-Treated Rats

Cited by 20 publications

References 43 publications

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

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

Prenatal expression of interleukin 1β and interleukin 6 in the rat pituitary gland

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