In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC: EGFP transgenic zebrafish

Sun, Lingli; Xu, Wei; He, Jiangyan; Yin, Zhan

doi:10.1016/j.taap.2010.08.015

Cited by 15 publications

(6 citation statements)

References 36 publications

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“…Here, we demonstrate using a series of chemical and environmental perturbations that alterations in cortisol levels affect the development of POMC cells from early stages. In agreement with previous studies, 11,16,17 we found that pituitary POMC cells, especially the anterior ACTH-producing corticotroph cluster were particularly sensitive to dexamethasone treatment. However, while earlier studies showed the effect of chronic dexamethasone treatment, our study employed quantitative methods to precisely establish a critical time window, during which the effect of dexamethasone is most pronounced.…”

Section: Discussionsupporting

confidence: 93%

“…Development of corticotrophs is sensitive to glucocorticoid levels at a critical developmental time windowWe next explored whether the effect of glucocorticoids on corticotroph cell clusters is restricted to a specific developmental time window. Previous studies examined the effect of chronic (4 days) dexamethasone treatment on corticotroph cells 11,16,17. To examine whether dexamethasone acts during a defined developmental window, we treated zebrafish larvae with dexamethasone at discrete time intervals and analyzed the effect on the POMC cell clusters.…”

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confidence: 99%

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Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Peles

Swaminathan

Levkowitz

2023

J Neuroendocrinology

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Corticotrophs are intermediaries in the hypothalamic–pituitary–adrenal (HPA) axis, which plays a crucial role in stress response in vertebrates. The HPA axis displays an intricate mode of negative feedback regulation, whereby the peripheral effector, cortisol inhibits the secretion of its upstream regulator, adrenocorticotropic hormone (ACTH) from proopiomelanocortin (POMC)‐expressing cells in the pituitary. While the feedback regulation of the HPA axis is well characterized in the adult organism, the effect of feedback regulation on the development of corticotrophs is poorly understood. Here, we studied the effect of glucocorticoids on the development of POMC‐expressing cells in the zebrafish pituitary. The development of POMC cells showed a steady increase in numbers between 2–6 days post fertilization. Inhibition of endogenous glucocorticoid synthesis resulted in an increase in POMC cell number due to reduced developmental feedback inhibition of cortisol on POMC cells. Conversely, addition of exogenous dexamethasone at a critical developmental window led to a decrease in corticotroph cell number, mimicking greater feedback control due to increased cortisol levels. Finally, developmental dysregulation of ACTH levels resulted in impaired anxiety‐like and stress‐coping behaviours. Hence, we identified a sensitive developmental window for the effect of glucocorticoids on corticotrophs and demonstrate the downstream effect on stress‐responsive behaviour.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Peles

Swaminathan

Levkowitz

2023

J Neuroendocrinology

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“…Significant reductions of pomc and cart transcript abundance were largely found in OBS-exposed zebrafish, raising the possibility that a reduced anorexigenic transcript abundance may have contributed to the lack of effect on food intake in OBS exposed larvae. Developmental pomc expression is centrally restricted to the anterior pituitary region, − allowing for a more precise interpretation of pomc gene expression changes in whole larvae compared to npy .…”

Section: Discussionmentioning

confidence: 99%

Bioconcentration and Metabolic Effects of Emerging PFOS Alternatives in Developing Zebrafish

Martínez

Navarro‐Martín

et al. 2019

Environ. Sci. Technol.

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The novel PFOS alternatives, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzenesulfonate (OBS), are emerging in the Chinese market, but little is known about their ecological risks. In this study, zebrafish embryos were exposed to PFOS, F-53B, and OBS to evaluate their bioconcentration and acute metabolic consequences. Per- and polyfluoroalkyl substances (PFASs) accumulated in larvae in the order of F-53B > PFOS > OBS, with the bioconcentration factors ranging from 20 to 357. Exposure to F-53B and PFOS, but not OBS, increased energy expenditure, and reduced feed intake in a concentration-dependent manner and the expression of genes involved in metabolic pathways at the transcriptional and translational levels. Molecular docking revealed that the binding affinities of PFASs to glucokinase were decreased in the following order: F-53B > PFOS > OBS. Finally, the results of Point of Departure (PoD) indicate that metabolic end points at the molecular and organismal level are most sensitive to F-53B followed by PFOS and OBS. Collectively, F-53B has the highest bioconcentration potential and the strongest metabolism-disrupting effects, followed by PFOS and OBS. Our findings have important implications for the assessment of early developmental metabolic effects of PFOS alternatives F-53B and OBS in wildlife and humans.

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“…Zebrafish larvae expressing GFP driven by an oxytocin promoter have been used to study the effect of fetal ethanol exposure on brain development, and as a model for fetal alcohol syndrome [70]. Also, POMC producing cells, an important component of the HPA, have been tagged in transgenic zebrafish lines [71,72]. In addition, zebrafish have been generated that express fluorescent proteins in GnRH, FSH, LH, and prolactin (PRL) secreting cells, which are deficient in PWS [73,74].…”

Section: Discussionmentioning

confidence: 99%

Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

et al. 2016

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Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients.

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In vivo alternative assessment of the chemicals that interfere with anterior pituitary POMC expression and interrenal steroidogenesis in POMC: EGFP transgenic zebrafish

Cited by 15 publications

References 36 publications

Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Glucocorticoid‐sensitive period of corticotroph development—Implications for mechanisms of early life stress

Bioconcentration and Metabolic Effects of Emerging PFOS Alternatives in Developing Zebrafish

Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics

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