Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells

Tian, Chunlei; Ye, Fei; Wang, Lei; Yuan-guo, Deng; Dong, Yuanxun; Wang, Xiaodan; Xu, Tong-jiang; Lei, Ting; Wang, Xiongwei

doi:10.1007/s12020-010-9402-9

Cited by 6 publications

(3 citation statements)

References 30 publications

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“…6f). These studies confirmed in our system the established roles in somatotrope proliferation of GHRHR (through G s ) and of GHSR (through G q/11 and G 12/13 ) 35,36 . For GPR101, the siRNA directed against G αs resulted in an unexpected increase in proliferation, which echoed the finding of increased phospho-ERK activity following G αs depletion described above (Fig.…”

Section: Resultssupporting

confidence: 87%

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

et al. 2020

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Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.

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Section: Resultssupporting

confidence: 87%

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

et al. 2020

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“…However, NO has been shown to act either as a friend or a foe towards cell cycle, in a dual or antagonistic manner as it does for cancer, exerting tumor promoting effects as well as anti‐tumoral effects [Choudhari et al, ]. For example, the NO‐donor s ‐nitroso‐ n ‐acetyl penicillamine (SNAP) has previously been reported to prevent cell cycle progression in many cell types: cerebellar glial cells [Garg et al ], BALB/C 3T3 fibroblasts [Garg and Hassid, ], endothelial cells [Sarkar et al, ], human airway smooth muscle cells [Hamad et al, ], lymphocytes [Kosonen et al, ], chick embryo retina glial cells [Magalhães et al, ], GH3 cells [Tian et al, ] and breast cancer cell lines MDA‐MB‐231 and MCF7 [Laudański et al, ]. By contrast, myoblasts were either stimulated or prevented in their proliferation, emphasizing the duality of NO towards cell proliferation [Ulibarri et al, ].…”

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confidence: 99%

Nitric Oxide Donor s‐Nitroso‐n‐Acetyl Penicillamine (SNAP) Alters Meiotic Spindle Morphogenesis in Xenopus Oocytes

Gelaude¹,

Marin²,

Cailliau³

et al. 2015

J of Cellular Biochemistry

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Nitric Oxide (NO) has been involved in both intra- and extra-cellular signaling pathways in a wide range of organisms, and can be detected in some reproductive tissues. Based upon previous results reporting that NO-donor SNAP (s-nitroso-n-acetyl penicillamine) promoted the release from the metaphase II-anaphase II block in amphibian eggs, the aim of the present study was to assess the influence of SNAP on the activation of the molecular mechanisms triggering meiotic resumption of Xenopus oocytes, analogous to G2/M transition of the cell cycle. A high concentration of SNAP (2.5 mM) was found to inhibit the appearance of the white spot (meiotic resumption) and promoted alteration of spindle morphogenesis leading to atypical structures lacking bipolarity and correct chromosomes equatorial alignment. The medium acidification (pH = 4) promoted by SNAP specifically impacted the white spot occurrence. However, even when pH was restored to 7.4 in SNAP medium, observed spindles remained atypical (microtubule disorganization), suggesting SNAP impacted spindle assembly regardless of the pH. n-Acetyl-d,l-penicillamine disulfide, a degradation product of SNAP with the same molecular characteristics, albeit without release of NO, yielded spindle assemblies typical of metaphase II suggesting the specificity of NO action on meiotic spindle morphogenesis in Xenopus oocytes.

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“…Previous studies have investigated the effect of ghrelin on breast, ovarian and gastric cancer cell lines, although contradictory results were generated (21)(22)(23)). An anti-proliferation effect has been documented in certain studies (24,25), whereas others have described a potential tumor-promoting role of ghrelin (26,27).…”

Section: Discussionmentioning

confidence: 99%

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas

Wang

Guo

Han

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Ghrelin, as a brain-gut peptide, has growth hormone (GH)-releasing and appetite-inducing activities and a widespread tissue distribution. Furthermore, ghrelin is an endogenous ligand of the GH secretagogue receptor (GHSR), and both ghrelin and GHSR are expressed in the pituitary; however, the data regarding the expression of ghrelin and GHSR in pituitary adenomas are divergent and conflicting. In the present study, therefore, the expression of ghrelin and GHSR was examined in the full spectrum of human pituitary adenoma subtypes (n=34) and in normal pituitary tissue (n=3). The mRNA and protein expression levels were quantified using a competitive reverse transcription-polymerase chain reaction and western blotting and the correlation of the results with the clinical parameters was assessed. mRNA and protein expression of ghrelin and GHSR was detected in all samples with the highest mean level in GH adenomas, a moderate level in clinically non-functioning adenomas and the lowest level in adrenocorticotropin adenomas. A significant correlation between the ghrelin and GHSR mRNA expression levels was observed in the GH adenomas (n=12) (r=0.8435, P=0.0006). The ghrelin mRNA expression level in the GH adenomas correlated positively with the basic serum GH level (n=12) (r=0.6488, P=0.0225). Furthermore, the mean level of ghrelin mRNA expression was significantly higher in invasive adenomas than in noninvasive adenomas (P<0.01). Collectively, the results of the study provided evidence that ghrelin and GHSR are expressed in the various subtypes of pituitary adenoma, with specific overexpression in GH adenomas. The study suggests that the binding of ghrelin to GHSR promotes the secretion of GH and plays an important role in the development of GH adenomas via autocrine and/or paracrine effects.

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Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells

Cited by 6 publications

References 30 publications

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

Nitric Oxide Donor s‐Nitroso‐n‐Acetyl Penicillamine (SNAP) Alters Meiotic Spindle Morphogenesis in Xenopus Oocytes

Correlation of ghrelin and growth hormone secretagogue receptor expression with clinical features in human pituitary adenomas

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