Cytokine-dependent gp130 receptor subunit regulates human fetal pituitary adrenocorticotropin hormone and growth hormone secretion.

Shimon, Ilan; Yan, Xinmin; Ray, David; Melmed, Shlomo

doi:10.1172/jci119541

Cited by 68 publications

(42 citation statements)

References 57 publications

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“…Their effects may result from direct action on the gastrointestinal system or indirect effects mediated by cytokines (ILβ-1, IL-2, IFN-γ and TNF-α) on the central nervous system. 12,[27][28][29][30][31][32][33] Cytokines can also interact with prostaglandins (members of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the body) and corticotrophin-releasing hormone (CRH), a polypeptide hormone and neurotransmitter involved in the stress response to inhibit gastric emptying. 29,30 Cytokine interaction with neuropeptides may induce anorexia and can also modify serotonin and catecholamine pathways in the central and peripheral nervous system.…”

Section: The Role Of Cytokinesmentioning

confidence: 99%

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Jurdana

2009

Radiology and Oncology

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Section: The Role Of Cytokinesmentioning

confidence: 99%

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Jurdana

2009

Radiology and Oncology

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“…We previously demonstrated LIF to be a potent auto͞paracrine stimulus of pituitary proopiomelanocortin (POMC) gene expression and adrenocorticotropic hormone (ACTH) secretion, modulating the hypothalamus-pituitary-adrenal (HPA) axis response to various inflammatory and stress stimuli (20)(21)(22). In vitro experiments using human fetal pituitary cells (23) and the corticotroph cell line AtT-20 (24,25) showed a profound synergistic action of LIF and corticotropin-releasing hormone on POMC gene expression and ACTH secretion. The LIF-induced signaling cascade in the corticotroph cell involves phosphorylation of gp130, STAT-3, and STAT-1 (15,23,26,27), and LIF-induced POMC expression and ACTH secretion is STAT-3 dependent (28).…”

mentioning

confidence: 94%

Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter

Auernhammer

Bousquet

Melmed

1999

Proc. Natl. Acad. Sci. U.S.A.

269

224

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Pituitary corticotroph SOCS-3 is a novel intracellular regulator of leukemia inhibitory factor (LIF)-mediated proopiomelanocortin gene expression and adrenocorticotropic hormone (ACTH) secretion, inhibiting LIF-activated Janus kinase-signal transducers and activators of transcription (STAT) signaling in a negative autoregulatory loop. We now demonstrate in corticotroph AtT-20 cells that LIF-stimulated endogenous SOCS-3 mRNA expression is blocked in stable transfectants of SOCS-3 wild type or in dominant negative STAT-3 mutants, respectively. We characterized Ϸ3.8-kb genomic 5 sequence of murine SOCS-3, including Ϸ2.9-kb sequence upstream of the transcription start site (؉1), which was determined by 5 rapid amplification of cDNA ends and RNase protection assay. Different 5 constructs were cloned into the pGL3Basic vector, and luciferase activity was assayed in transiently transfected ACTH-secreting corticotroph AtT-20 cells. A STAT-1͞STAT-3 binding element, located at nucleotides ؊72 to ؊64, was essential for LIF stimulation of SOCS-3 promoter activity. LIF induced 10-fold increased luciferase activity in a wild-type construct spanning ؊2757 to ؉929 bases. However, deletion or point mutation of the STAT-1͞STAT-3 binding element abrogated LIF action (2-to 3-fold). Electrophoretic mobility-shift assay analysis confirmed specific binding of STAT-1 and STAT-3 to this region. These results characterize the genomic 5 region of murine SOCS-3 and identify an important STAT-1͞STAT-3 binding element therein. Thus, LIFstimulated SOCS-3 gene expression is at least in part mediated by STAT-3 and STAT-1. The cytokine inhibitor SOCS-3 acts in a negative loop to autoregulate its own gene expression, thus limiting its accumulation in the corticotroph cell. These results demonstrate a mechanism for corticotroph plasticity with rapid

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“…gp130 expression is ubiquitous, and its ability to respond differentially to each of the proteins that belong to the gp130 cytokine family is determined by the expression of the cytokines or their specific alpha receptor chains. This occurs also in the pituitary gland, where many studies have demonstrated not only the expression of gp130 mRNA (6) but also the expression of specific receptors and synthesis of gp130 cytokines in different types of pituitary cells (reviewed in [7][8][9][10], providing the cellular and molecular basis for an auto-paracrine mechanism of regulation of pituitary function. Particularly, several groups have demonstrated IL-6 production and the presence of IL-6 mRNA in anterior pituitary cells (11,12).…”

Section: Introductionmentioning

confidence: 99%

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

Graciarena

Carbia-Nagashima²,

Onofri

et al. 2004

European Journal of Endocrinology

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Objective: gp130 cytokines are placed as auto-paracrine regulators of pituitary function, since they, as well as their receptors, have been shown to be expressed in and to act in normal and tumoral anterior pituitary cells. The objective of this work was to study their involvement in a model that shows the interaction between different cellular types that participate in a tumorigenic process. Design: The dependence of a pituitary somatotrophic cell line (MtT/S) on a gp130 cytokine-producing folliculostellate (FS) cell line (TtT/GF) for tumorigenesis in vivo has been described. In order to study the participation of gp130 cytokines in the auto-paracrine stimulation of MtT/S growth, we generated MtT/S gp130 sense (gp130-S) and gp130 antisense (gp130-AS) clones stably transfected with pcDNA3/gp130 sense and pcDNA3/gp130 antisense vectors respectively. Methods and results: Functional characterization studies revealed that gp130-AS clones have an inhibited gp130 signalling, and proliferation studies showed that they have an impaired response to gp130 cytokines but respond normally to other independent stimuli. When injected into nude mice, MtT/S clones respond differently depending on cell number; at high concentrations MtT/S clones alone generated tumours equivalent in size to tumours derived from MtT/S plus TtT/GF cells. At low concentrations, MtT/S sense and control clones generated tumours of smaller size than tumours derived from these same clones plus TtT/GF cells, showing a dependence on FS cells. In both cases MtT/S gp130-AS clones had impaired tumour development. Furthermore, vessel density was significantly lower in tumours derived from gp130-AS plus TtT/GF cells. Conclusions: This study underlines the importance of gp130 cytokines in proliferation and establishes its role in auto-paracrine pituitary growth regulation.European Journal of Endocrinology 151 595-604

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Cytokine-dependent gp130 receptor subunit regulates human fetal pituitary adrenocorticotropin hormone and growth hormone secretion.

Abstract: We have shown recently that leukemia inhibitory factor (LIF) and oncostatin M (OSM), two members of the gp130-dependent cytokine family, stimulate murine proopiomelanocortin (

Cited by 68 publications

References 57 publications

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Cancer cachexia-anorexia syndrome and skeletal muscle wasting

Autoregulation of pituitary corticotroph SOCS-3 expression: Characterization of the murine SOCS-3 promoter

Involvement of the gp130 cytokine transducer in MtT/S pituitary somatotroph tumour development in an autocrine-paracrine model

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