Effects of corticotrophin-releasing hormone, vasopressin and insulin-like growth factor-I on proliferation of and adrenocorticotrophic hormone secretion by canine corticotrophic adenoma cells in vitro

Wijk, P. A. Van; Rijnberk, A.; Croughs, R. J. M.; Meij, Björn P.; Mol, Jan A.

doi:10.1530/eje.0.1380309

Cited by 13 publications

(6 citation statements)

References 49 publications

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“…In the present study, treatment with RAd-IGF-I induced a significant decrease in ACTH cell size without changes in the cell density compared to estrogen + Rad-GFP treatment. These data agree with the findings of Van Wijk et al [1998], who reported that intrapituitary IGF-I does not have growth-stimulating effects on canine corticotropic tumor cells.…”

Section: Discussionsupporting

confidence: 93%

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

Camihort¹,

Hereñú

Luna

et al. 2009

Cells Tissues Organs

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In previous studies, we assessed the effects of intrapituitary injection of a recombinant adenoviral vector (RAd) harboring the cDNA for rat insulin-like growth factor type I (RAd-IGF-I) on the lactotrope and somatotrope populations in estrogen-induced prolactinomas. In the present study, we aimed to confirm these findings and further analyze the effect of transgenic RAd-IGF-I on the other pituitary cell populations in female rats. All animals except the intact group (no estrogen and no stereotaxic injection) received subcutaneous estrogen for 30 days, and the groups which received RAd-IGF-I or RAd expressing green fluorescent protein (control) were additionally treated with the appropriate vectors on experimental day 0. The RAd-IGF-I group showed a significant decrease in serum growth hormone and prolactin levels and lactotrope and somatotrope cell size induced by estrogen treatment. Cell density was not affected by 7 days of IGF-I gene therapy. Estrogen had an inhibitory effect on thyrotrope cell density, whereas with RAd-IGF-I there was a nonsignificant trend towards restoration of cell density, without changes in cell size. RAd-IGF-I treatment decreased corticotrope cell size without changing cell density. Estrogen decreased gonadotrope cell size and density, which was reversed by RAd-IGF-I. We conclude that in estrogen-induced pituitary tumors, IGF-I gene therapy has inhibitory effects on the lactotrope, somatotrope and corticotrope populations, while reversing the effect of estrogen on gonadotropic cells.

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Section: Discussionsupporting

confidence: 93%

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

Camihort¹,

Hereñú

Luna

et al. 2009

Cells Tissues Organs

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“…However, in the present work we found that in 4T1 cells CRF induced cell proliferation, whereas in MCF7, and others cell lines such as the adenocarcinoma cell line Ishikawa and the human HaCaT keratinocytes [18,24,25], proliferation was suppressed by CRF. In contrast, CRF induced proliferation of the At20 corticotrophic adenocarcinoma cell line and primary canine corticotrophic adenoma cells [40,41]. This discrepancy is in accordance with previous works describing that the phenotypic effects of CRF on cell proliferation were dependent on both cell type and nutrition conditions [42].…”

Section: Discussionsupporting

confidence: 85%

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

et al. 2010

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IntroductionStress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF) is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo.MethodsFor this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis.ResultsArray analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo.ConclusionThis is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and β-catenin expression.

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“…From this perspective, the establishment of transsphenoidal hypophysectomy as an accepted treatment for canine CD may have opened up a new source of valuable primary corticotroph tissue, which could overcome some of the these obstacles [6, 7]. Van Wijk et al have shown previously that canine corticotroph adenoma cells cultured in vitro retain important biological properties, such as the production of ACTH, and a variable responsiveness to both corticotropin-releasing hormone and glucocorticoids, just like human corticotroph adenoma cells in vitro [8]. Canine corticotroph adenomas also have been used to study fundamental aspects of the impaired feedback regulation of the glucocorticoid receptor in CD [9].…”

Section: Discussionmentioning

confidence: 99%

Cushing’s Disease in Dogs and Humans

et al. 2009

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Background: Cushing’s disease (CD) is a common endocrinological disorder in dogs with an estimated incidence of 1 to 2 cases/1,000 dogs/year. This is in contrast to humans in whom CD is rare. The clinical presentation of CD, however, is highly similar between dogs and humans, with characteristic signs, such as abdominal obesity, weight gain, fatigue, muscle atrophy and skin changes. Canine CD may therefore serve as an animal model for human CD, especially since therapeutic canine hypophysectomy can generate substantial amounts of primary corticotroph adenoma tissue for in vitro research purposes. In a recent study, we found that dopamine (DA) D₂ and somatostatin (SS) receptor subtypes are well expressed in canine corticotroph adenomas, but there are some distinct differences compared with the expression profile observed in human CD. These differences need to be considered when using canine CD as a model to evaluate the efficacy of novel DA/SS compounds for potential use in human CD. Case Report: This case involves an 8-year-old female dog that developed signs of exercise intolerance, muscle weakness and polyuria/polydipsia due to an adrenocorticotropic hormone-secreting pituitary adenoma. The dog underwent curative transsphenoidal hypophysectomy and has remained in complete remission in the 3.5 years since surgery.

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Effects of corticotrophin-releasing hormone, vasopressin and insulin-like growth factor-I on proliferation of and adrenocorticotrophic hormone secretion by canine corticotrophic adenoma cells in vitro

Cited by 13 publications

References 49 publications

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

Cushing’s Disease in Dogs and Humans

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