scholarly journals Small Molecule Agonists of the Orphan Nuclear Receptors Steroidogenic Factor-1 (SF-1, NR5A1) and Liver Receptor Homologue-1 (LRH-1, NR5A2)

2011 ◽  
Vol 54 (7) ◽  
pp. 2266-2281 ◽  
Author(s):  
Richard J. Whitby ◽  
Jozef Stec ◽  
Raymond D. Blind ◽  
Sally Dixon ◽  
Lisa M. Leesnitzer ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Small Molecule ◽  
Orphan Nuclear Receptors ◽  
Steroidogenic Factor 1

Identification of Small Molecule Agonists of the Orphan Nuclear Receptors Liver Receptor Homolog-1 and Steroidogenic Factor-1

2006 ◽  
Vol 49 (23) ◽  
pp. 6652-6655 ◽  
Author(s):  
Richard J. Whitby ◽  
Sally Dixon ◽  
Patrick R. Maloney ◽  
Philippe Delerive ◽  
Bryan J. Goodwin ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Small Molecule ◽  
Orphan Nuclear Receptors ◽  
Steroidogenic Factor 1

scholarly journals The Orphan Nuclear Receptors Steroidogenic Factor-1 and Liver Receptor Homolog-1: Structure, Regulation, and Essential Roles in Mammalian Reproduction

2019 ◽  
Vol 99 (2) ◽  
pp. 1249-1279 ◽  
Author(s):  
Marie-Charlotte Meinsohn ◽  
Olivia E. Smith ◽  
Kalyne Bertolin ◽  
Bruce D. Murphy
Keyword(s):  
Cancer Cells ◽  
Nuclear Receptors ◽  
Leydig Cell ◽  
Dna Sequences ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Specific Cell ◽  
Orphan Nuclear Receptors ◽  
Steroidogenic Factor 1 ◽  
Estrogen Synthesis

Nuclear receptors are intracellular proteins that act as transcription factors. Proteins with classic nuclear receptor domain structure lacking identified signaling ligands are designated orphan nuclear receptors. Two of these, steroidogenic factor-1 (NR5A1, also known as SF-1) and liver receptor homolog-1 (NR5A2, also known as LRH-1), bind to the same DNA sequences, with different and nonoverlapping effects on targets. Endogenous regulation of both is achieved predominantly by cofactor interactions. SF-1 is expressed primarily in steroidogenic tissues, LRH-1 in tissues of endodermal origin and the gonads. Both receptors modulate cholesterol homeostasis, steroidogenesis, tissue-specific cell proliferation, and stem cell pluripotency. LRH-1 is essential for development beyond gastrulation and SF-1 for genesis of the adrenal, sexual differentiation, and Leydig cell function. Ovary-specific depletion of SF-1 disrupts follicle development, while LRH-1 depletion prevents ovulation, cumulus expansion, and luteinization. Uterine depletion of LRH-1 compromises decidualization and pregnancy. In humans, SF-1 is present in endometriotic tissue, where it regulates estrogen synthesis. SF-1 is underexpressed in ovarian cancer cells and overexpressed in Leydig cell tumors. In breast cancer cells, proliferation, migration and invasion, and chemotherapy resistance are regulated by LRH-1. In conclusion, the NR5A orphan nuclear receptors are nonredundant factors that are crucial regulators of a panoply of biological processes, across multiple reproductive tissues.

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
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