Orphan Nuclear Receptors, Molecular Clockwork, and the Entrainment of Peripheral Oscillators

2008 ◽  
pp. 89-101 ◽  
Author(s):  
Nicolas Preitner ◽  
Steven Brown ◽  
Juergen Ripperger ◽  
Nguyet Le-Minh ◽  
Francesca Damiola ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Orphan Nuclear Receptors ◽  
Peripheral Oscillators

Local Regulation of Adrenal Steroidogenesis: Subtle in vitro Effects of IL-1β on the Human Cell Line NCI-H295R Steroid Production along with Changes in MicroRNA Profile and Orphan Nuclear Receptors NR4As

2021 ◽  
pp. 1-11
Author(s):  
Natalia Santucci ◽  
Rocío Stampone ◽  
Eduardo Brandão Ferreira da Silva ◽  
Silvina Villar ◽  
Silvana Spinelli ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cell Line ◽  
Nuclear Receptors ◽  
Human Cell ◽  
Human Cell Line ◽  
Mirna Profile ◽  
Orphan Nuclear Receptors ◽  
Steroid Production ◽  
Adrenal Steroid ◽  
Adrenal Steroidogenesis

<b><i>Introduction:</i></b> IL-1β, a cytokine from the innate immune response, is well known for its proinflammatory effects and stimulating activity on the hypothalamus-pituitary-adrenal axis, leading to the pituitary synthesis of adrenocorticotropic hormone followed by cortisol (and dehydroepiandrosterone – DHEA) release by the adrenal gland. While IL-1β modulates the adrenal steroidogenesis at the central level, it is unclear whether it also exerts an effect on the adrenal gland. <b><i>Method:</i></b> We studied the effect of IL-1β on adrenal steroid production and steroidogenic enzyme RNA expression in the human cell line NCI-H295R. We also explored eventual changes in the microRNA (miRNA) profile from IL-1β-treated NCI-H295R cells. <b><i>Results:</i></b> Transcripts encoding IL-1β receptors 1 and 2 were noticeable in the cell line, with cortisol and DHEA production showing a subtle increase after cytokine treatment. Transcripts from key enzymes in the steroidogenic pathway were analyzed, with no noticeable changes on them. The miRNA profile was modified by IL-1β treatment to an extent which bears some relationship with the regulatory mechanisms underlying adrenal steroid production. Since orphan nuclear receptors NR4As have emerged as potential key factors for coordinating inflammatory and metabolic responses, cell expression studies were also carried out to show an NR4As transcript augmentation following IL-1β treatment. <b><i>Discussion/Conclusions:</i></b> The subtle increase in adrenal steroid production in response to IL-1β stimulation without any modification in the transcription of the steroidogenic enzymes analyzed suggests an additional inflammatory/anti-inflammatory loop, wherein NR4As receptors may participate. Besides its physiological role, this process might be implied in pathological states accompanied by an unbalanced immune-endocrine relationship.

The NR4A family of orphan nuclear receptors are not required for adipogenesis

2007 ◽  
Vol 32 (2) ◽  
pp. 388-392 ◽  
Author(s):  
W-S Au ◽  
V A Payne ◽  
S O'Rahilly ◽  
J J Rochford
Keyword(s):  
Nuclear Receptors ◽  
Orphan Nuclear Receptors

scholarly journals ONRLDB—manually curated database of experimentally validated ligands for orphan nuclear receptors: insights into new drug discovery

Database ◽  
2015 ◽  
Vol 2015 ◽  
pp. bav112 ◽  
Author(s):  
Ravikanth Nanduri ◽  
Isha Bhutani ◽  
Arun Kumar Somavarapu ◽  
Sahil Mahajan ◽  
Raman Parkesh ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Nuclear Receptors ◽  
Orphan Nuclear Receptors ◽  
New Drug

Emerging roles of orphan nuclear receptors in regulation of innate immunity

2016 ◽  
Vol 39 (11) ◽  
pp. 1491-1502 ◽  
Author(s):  
Hyo Sun Jin ◽  
Tae Sung Kim ◽  
Eun-Kyeong Jo
Keyword(s):  
Innate Immunity ◽  
Nuclear Receptors ◽  
Orphan Nuclear Receptors

scholarly journals Function of Nr4a Orphan Nuclear Receptors in Proliferation, Apoptosis and Fuel Utilization Across Tissues

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1373 ◽  
Author(s):  
Herring ◽  
Elison ◽  
Tessem
Keyword(s):  
Transcription Factors ◽  
Family Member ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Cellular Proliferation ◽  
Nuclear Hormone Receptors ◽  
Fuel Utilization ◽  
Orphan Nuclear Receptors ◽  
Tissue Specific ◽  
Specific Effects

The Nr4a family of nuclear hormone receptors is composed of three members—Nr4a1/Nur77, Nr4a2/Nurr1 and Nr4a3/Nor1. While currently defined as ligandless, these transcription factors have been shown to regulate varied processes across a host of tissues. Of particular interest, the Nr4a family impinge, in a tissue dependent fashion, on cellular proliferation, apoptosis and fuel utilization. The regulation of these processes occurs through both nuclear and non-genomic pathways. The purpose of this review is to provide a balanced perspective of the tissue specific and Nr4a family member specific, effects on cellular proliferation, apoptosis and fuel utilization.

scholarly journals Targeting Orphan Nuclear Receptors NR4As for Energy Homeostasis and Diabetes

2020 ◽  
Vol 11 ◽  
Author(s):  
Chenyang Zhang ◽  
Bin Zhang ◽  
Xuelian Zhang ◽  
Guibo Sun ◽  
Xiaobo Sun
Keyword(s):  
Nuclear Receptors ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Orphan Nuclear Receptors ◽  
Critical Function ◽  
Carbohydrate And Lipid Metabolism ◽  
Regulatory Effects ◽  
Treatment Of Obesity ◽  
Nuclear Receptor Family ◽  
Receptor Family

Orphan nuclear receptors are important members of the nuclear receptor family and may regulate cell proliferation, metabolism, differentiation, and apoptosis. NR4As, a subfamily of orphan nuclear receptors, have been reported to play key roles in carbohydrate and lipid metabolism and energy homeostasis. Popularity of obesity has resulted in a series of metabolic diseases such as diabetes and its complications. While imbalance of energy intake and expenditure is the main cause of obesity, the concrete mechanism of obesity has not been fully understood. It has been reported that NR4As have significant regulatory effects on energy homeostasis and diabetes and are expected to become new targets for discovering drugs for metabolic syndrome. A number of studies have demonstrated that abnormalities in metabolism induced by altered levels of NR4As may contribute to numerous diseases, such as chronic inflammation, tumorigenesis, diabetes and its complications, atherosclerosis, and other cardiovascular diseases. However, systematic reviews focusing on the roles of NR4As in mediating energy homeostasis and diabetes remain limited. Therefore, this article reviews the structure and regulation of NR4As and their critical function in energy homeostasis and diabetes, as well as small molecules that may regulate NR4As. Our work is aimed at providing valuable support for the research and development of drugs targeting NR4As for the treatment of obesity and related metabolic diseases.

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