gp130 cytokine signaling in the pituitary gland: a paradigm for cytokine–neuro-endocrine pathways

Arzt, Eduardo

doi:10.1172/jci200114660

Cited by 68 publications

(29 citation statements)

References 43 publications

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“…Inhibitory or stimulatory actions of R246 Review m sapochnik and others IL-6 and pituitary senescence 58 4 : R246 Review IL-6 were observed in ACTH-, PRL-, GH-secreting and nonfunctioning adenomas, without association to the size or type of the tumor (Pereda et al 1996). Activation of different signaling pathways by IL-6/gp130 complex, as discussed previously, may explain the differences observed in IL-6 action on the anterior pituitary (Arzt 2001).…”

Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 81%

“…It acts as a stimulatory growth factor , Arzt 2001) and also promotes the secretion of vascular endothelial growth factor and matrix metalloproteinases from surrounding FS cells (Renner et al 1998, Gloddek et al 1999, producing not only the expansion of tumoral cells but also vessel formation and extracellular matrix remodeling (Renner et al 1998). Notably, although this cytokine induced proliferation of GH3 lactosomatotroph cells, it was also shown to inhibit normal pituitary cells (Arzt et al 1993).…”

Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 99%

“…Pituitary tumorigenesis appears to be regulated by extrinsic and intrinsic factors. It has been demonstrated that paracrine IL-6's effects may allow initial pituitary cell growth (required for senescence bypass) , Arzt 2001, Graciarena et al 2004, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation (Sapochnik et al 2016). This review provides an insight into the current understanding of the role of IL-6 in the regulation of pituitary pathogenesis, focusing in the autocrine action of IL-6.…”

Section: Introductionmentioning

confidence: 99%

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Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

Fuertes

Arzt

2017

Journal of Molecular Endocrinology

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IL-6 is a pleiotropic cytokine with multiple pathophysiological functions. As a key factor of the senescence secretome, it can not only promote tumorigenesis and cell proliferation but also exert tumor suppressive functions, depending on the cellular context. IL-6, as do other cytokines, plays important roles in the function, growth and neuroendocrine responses of the anterior pituitary gland. The multiple actions of IL-6 on normal and adenomatous pituitary function, cell proliferation, angiogenesis and extracellular matrix remodeling indicate its importance in the regulation of the anterior pituitary. Pituitary tumors are mostly benign adenomas with low mitotic index and rarely became malignant. Premature senescence occurs in slow-growing benign tumors, like pituitary adenomas. The dual role of IL-6 in senescence and tumorigenesis is well represented in pituitary tumor development, as it has been demonstrated that effects of paracrine IL-6 may allow initial pituitary cell growth, whereas autocrine IL-6 in the same tumor triggers senescence and restrains aggressive growth and malignant transformation. IL-6 is instrumental in promotion and maintenance of the senescence program in pituitary adenomas.

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Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 81%

Section: Pathophysiological Role Of Il-6 In the Pituitarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Programmed cell senescence: role of IL-6 in the pituitary

Sapochnik

Fuertes

Arzt

2017

Journal of Molecular Endocrinology

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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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“…This constitutes the basis for the paracrine and autocrine action of cytokines in the control of hormone production and cell proliferation in the pituitary (11)(12)(13)(14)(15). Growth factors and hypothalamic factors also play a part in the molecular and cellular mechanisms that lead to prolactinoma development (11)(12)(13). Bone morphogenetic proteins (BMPs), as well as other members of the type ␤ transforming growth factor (TGF␤) family, transduce signals through Smad4, a signal cotransducer (16)(17)(18).…”

mentioning

confidence: 99%