Molecular Biology of Glucocorticoid Signaling

Arango-Lievano, Margarita; Lambert, W. Marcus; Jeanneteau, Freddy

doi:10.1007/978-1-4939-2895-8_2

Cited by 25 publications

(22 citation statements)

References 146 publications

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“…Glucocorticoids effects on mitochondria and synapses depend on the dose, duration, and context at exposure [ 121 ]. The effects of dose and duration recapitulated by the acute and chronic stress paradigms were discussed earlier.…”

Section: Context-dependent Glucocorticoid Signaling: Bdnf Is Contementioning

confidence: 99%

“…The effects of dose and duration recapitulated by the acute and chronic stress paradigms were discussed earlier. The context at exposure such as learning at the time of glucocorticoid oscillation peak could produce unique effects, temporally restricted, that are the results of the coupling of neuronal activity with glucocorticoid signaling in select neuronal networks [ 64 , 121 ]. For example, a single injection of glucocorticoids within minutes of motor skill training enhanced motor learning.…”

Section: Context-dependent Glucocorticoid Signaling: Bdnf Is Contementioning

confidence: 99%

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Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders

Jeanneteau

Arango-Lievano

2016

Neural Plasticity

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The brain evolved cellular mechanisms for adapting synaptic function to energy supply. This is particularly evident when homeostasis is challenged by stress. Signaling loops between the mitochondria and synapses scale neuronal connectivity with bioenergetics capacity. A biphasic “inverted U shape” response to the stress hormone glucocorticoids is demonstrated in mitochondria and at synapses, modulating neural plasticity and physiological responses. Low dose enhances neurotransmission, synaptic growth, mitochondrial functions, learning, and memory whereas chronic, higher doses produce inhibition of these functions. The range of physiological effects by stress and glucocorticoid depends on the dose, duration, and context at exposure. These criteria are met by neuronal activity and the circadian, stress-sensitive and ultradian, stress-insensitive modes of glucocorticoid secretion. A major hallmark of stress-related neuropsychiatric disorders is the disrupted glucocorticoid rhythms and tissue resistance to signaling with the glucocorticoid receptor (GR). GR resistance could result from the loss of context-dependent glucocorticoid signaling mediated by the downregulation of the activity-dependent neurotrophin BDNF. The coincidence of BDNF and GR signaling changes glucocorticoid signaling output with consequences on mitochondrial respiration efficiency, synaptic plasticity, and adaptive trajectories.

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Section: Context-dependent Glucocorticoid Signaling: Bdnf Is Contementioning

confidence: 99%

Section: Context-dependent Glucocorticoid Signaling: Bdnf Is Contementioning

confidence: 99%

Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders

Jeanneteau

Arango-Lievano

2016

Neural Plasticity

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“…glucocorticoid response elements, or GREs) of target genes, and alter gene expression. GR target genes may comprise more than 10% of the genome and include those involved in metabolism, immunity, and cell survival and growth, among others 7 . For example, in white adipose tissue (WAT) of terrestrial mammals, GCs increase fatty acid availability and adipocyte differentiation by upregulating expression of lipases and pro-adipogenesis factors (e.g.…”

mentioning

confidence: 99%

Blubber transcriptome response to acute stress axis activation involves transient changes in adipogenesis and lipolysis in a fasting-adapted marine mammal

Khudyakov

Champagne

Meneghetti

et al. 2017

Sci Rep

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Stress can compromise an animal’s ability to conserve metabolic stores and participate in energy-demanding activities that are critical for fitness. Understanding how wild animals, especially those already experiencing physiological extremes (e.g. fasting), regulate stress responses is critical for evaluating the impacts of anthropogenic disturbance on physiology and fitness, key challenges for conservation. However, studies of stress in wildlife are often limited to baseline endocrine measurements and few have investigated stress effects in fasting-adapted species. We examined downstream molecular consequences of hypothalamic-pituitary-adrenal (HPA) axis activation by exogenous adrenocorticotropic hormone (ACTH) in blubber of northern elephant seals due to the ease of blubber sampling and its key role in metabolic regulation in marine mammals. We report the first phocid blubber transcriptome produced by RNAseq, containing over 140,000 annotated transcripts, including metabolic and adipocytokine genes of interest. The acute response of blubber to stress axis activation, measured 2 hours after ACTH administration, involved highly specific, transient (lasting <24 hours) induction of gene networks that promote lipolysis and adipogenesis in mammalian adipocytes. Differentially expressed genes included key adipogenesis factors which can be used as blubber-specific markers of acute stress in marine mammals of concern for which sampling of other tissues is not possible.

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“…Glucocorticoids (GCs) are essential for survival and serve a major role in embryonic development, tissue homeostasis and in the regulation of the inflammatory response ( 1 , 2 ). In breast, the functions of GCs are complex and depend, in part, if they are linked to their receptor (GR) and consist of the control of milk secretion, differentiation and apoptosis ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of the glucocorticoid receptor in breast cancer-associated fibroblasts

Catteau

Simon

Buxant

et al. 2016

Molecular and Clinical Oncology

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Cancer- associated fibroblasts (CAFs) are actively involved in breast carcinoma. Our previous study demonstrated that the majority of these CAFs were smooth muscle actin (SMA) positive and were therefore termed peritumoral myofibroblast (PMY). Glucocorticoid, linked or not with its receptor (GR), has been postulated to serve a major role in normal breast and breast carcinoma; however, their role in CAFs remains poorly understood. The aim of the present study was to assess the presence of GR in breast CAFs and particularly in PMY in 56 cases of invasive breast carcinoma in correlation with clinicopathological parameters, by immunohistochemistry. GR was observed in CAFs in 51 cases (91%) and were more frequent in luminal A subtype (19/19 cases; 100%). The stromal expression was statistically correlated with the tumor grade (P=0.03), the Ki-67 index (P=0.003) and the presence of GR in the epithelial component (P=0.01). The demonstration of a frequent expression of GR in breast CAFs may serve as an interesting target for future therapeutics for the regulation of the tumoral breast microenvironment.

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Molecular Biology of Glucocorticoid Signaling

Cited by 25 publications

References 146 publications

Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders

Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders

Blubber transcriptome response to acute stress axis activation involves transient changes in adipogenesis and lipolysis in a fasting-adapted marine mammal

Expression of the glucocorticoid receptor in breast cancer-associated fibroblasts

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