Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction

Reproduction ◽  
2005 ◽  
Vol 129 (4) ◽  
pp. 379-389 ◽  
Author(s):  
P Pocar ◽  
B Fischer ◽  
T Klonisch ◽  
S Hombach-Klonisch
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Reproductive Tract ◽  
Wide Spectrum ◽  
Environmental Pollutants ◽  
Large Body ◽  
Female Reproductive Tract ◽  
Female Reproduction ◽  
Aryl Hydrocarbon

The dioxin/aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsive to both natural and man-made environmental compounds. AhR and its nuclear partner ARNT are expressed in the female reproductive tract in a variety of species and several indications suggest that the AhR might play a pivotal role in the physiology of reproduction. Furthermore, it appears to be the mediator of most, if not all, the adverse effects on reproduction of a group of highly potent environmental pollutants collectively called aryl hydrocarbons (AHs), including the highly toxic compound 2,3,7,8-tetrachlor-odibenzo-p-dioxin (TCDD). Although a large body of recent literature has implicated AhR in multiple signal transduction pathways, the mechanisms of action resulting in a wide spectrum of effects on female reproduction are largely unknown. Here we summarize the major types of molecular cross-talks that have been identified for the AhR and linked cell signaling pathways and that are relevant for the understanding of the role of this transcription factor in female reproduction.

scholarly journals A Protective Role of Aryl Hydrocarbon Receptor Repressor in Inflammation and Tumor Growth

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 589 ◽  
Author(s):  
Christoph F. A. Vogel ◽  
Yasuhiro Ishihara ◽  
Claire E. Campbell ◽  
Sarah Y. Kado ◽  
Aimy Nguyen-Chi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Aryl Hydrocarbon Receptor ◽  
Inflammatory Responses ◽  
Environmental Pollutants ◽  
Protective Role ◽  
Potential Therapeutic Target ◽  
Embryonic Fibroblasts ◽  
Aryl Hydrocarbon ◽  
Enhancer Binding Protein

The aryl hydrocarbon receptor (AhR) is known for mediating the toxicity of environmental pollutants such as dioxins and numerous dioxin-like compounds, and is associated with the promotion of various malignancies, including lymphoma. The aryl hydrocarbon receptor repressor (AhRR), a ligand-independent, transcriptionally inactive AhR-like protein is known to repress AhR signaling through its ability to compete with the AhR for dimerization with the AhR nuclear translocator (ARNT). While AhRR effectively blocks AhR signaling, several aspects of the mechanism of AhRR’s functions are poorly understood, including suppression of inflammatory responses and its putative role as a tumor suppressor. In a transgenic mouse that overexpresses AhRR (AhRR Tg) we discovered that these mice suppress 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)- and inflammation-induced tumor growth after subcutaneous challenge of EL4 lymphoma cells. Using mouse embryonic fibroblasts (MEF) we found that AhRR overexpression suppresses the AhR-mediated anti-apoptotic response. The AhRR-mediated inhibition of apoptotic resistance was associated with a suppressed expression of interleukin (IL)-1β and cyclooxygenase (COX)-2, which was dependent on activation of protein kinase A (PKA) and the CAAT-enhancer-binding protein beta (C/EBPβ). These results provide mechanistic insights into the role of the AhRR to suppress inflammation and highlight the AhRR as a potential therapeutic target to suppress tumor growth.

scholarly journals Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor

2020 ◽  
Vol 21 (10) ◽  
pp. 3486 ◽  
Author(s):  
Wen-Chih Liu ◽  
Jia-Fwu Shyu ◽  
Paik Seong Lim ◽  
Te-Chao Fang ◽  
Chien-Lin Lu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Indoxyl Sulfate ◽  
Raw 264.7 Cells ◽  
High Dose ◽  
Activated T Cells ◽  
Aryl Hydrocarbon

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.

scholarly journals Trajectory Shifts in Interdisciplinary Research of the Aryl Hydrocarbon Receptor—A Personal Perspective on Thymus and Skin

2021 ◽  
Vol 22 (4) ◽  
pp. 1844
Author(s):  
Charlotte Esser
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Environmental Pollution ◽  
Aryl Hydrocarbon Receptor ◽  
Interdisciplinary Research ◽  
Adaptive Response ◽  
Personal Perspective ◽  
Aryl Hydrocarbon

Identifying historical trajectories is a useful exercise in research, as it helps clarify important, perhaps even “paradigmatic”, shifts in thinking and moving forward in science. In this review, the development of research regarding the role of the transcription factor “aryl hydrocarbon receptor” (AHR) as a mediator of the toxicity of environmental pollution towards a link between the environment and a healthy adaptive response of the immune system and the skin is discussed. From this fascinating development, the opportunities for targeting the AHR in the therapy of many diseases become clear.

scholarly journals The Aryl Hydrocarbon Receptor Relays Metabolic Signals to Promote Cellular Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Fanny L. Casado
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Transcription Factor ◽  
Regenerative Medicine ◽  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathways ◽  
Metabolic Efficiency ◽  
Aryl Hydrocarbon ◽  
Cellular Regeneration

While sensing the cell environment, the aryl hydrocarbon receptor (AHR) interacts with different pathways involved in cellular homeostasis. This review summarizes evidence suggesting that cellular regeneration in the context of aging and diseases can be modulated by AHR signaling on stem cells. New insights connect orphaned observations into AHR interactions with critical signaling pathways such as WNT to propose a role of this ligand-activated transcription factor in the modulation of cellular regeneration by altering pathways that nurture cellular expansion such as changes in the metabolic efficiency rather than by directly altering cell cycling, proliferation, or cell death. Targeting the AHR to promote regeneration might prove to be a useful strategy to avoid unbalanced disruptions of homeostasis that may promote disease and also provide biological rationale for potential regenerative medicine approaches.

scholarly journals The aryl hydrocarbon receptor and the gut–brain axis

2021 ◽  
Author(s):  
Andreia Barroso ◽  
João Vitor Mahler ◽  
Pedro Henrique Fonseca-Castro ◽  
Francisco J. Quintana
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Potential Value ◽  
Aryl Hydrocarbon ◽  
Immune Mediated ◽  
Health And Disease

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

scholarly journals Endoscopy in the management of a rudimentary non-communicating functional horn

2019 ◽  
Vol 8 (2) ◽  
pp. 783
Author(s):  
Nitin H. Shah ◽  
Aditi V. Joshi ◽  
Sunita Mourya
Keyword(s):  
Rare Variant ◽  
Reproductive Tract ◽  
Wide Spectrum ◽  
Female Reproductive Tract ◽  
Young Adolescent ◽  
Septate Uterus ◽  
Unicornuate Uterus ◽  
Post Surgery ◽  
Mullerian Anomaly

Mullerian anomalies are developmental malformations of the female reproductive tract, often diagnosed late. They are classified into numerous types like a septate uterus, bicornuate or unicornuate uterus etc. A rudimentary non-communicating functional horn is a rare variant of a unicornuate uterus. It may present with a wide spectrum of symptoms like severe dysmenorrhea, infertility, lump in abdomen or rarely maybe diagnosed with a ruptured ectopic in the horn. The diagnosis of this entity is a difficult and challenging. Authors present a case of a young adolescent diagnosed with this Mullerian anomaly, the role of hysteroscopy in confirmation of diagnosis and the management of the patient by laparoscopy successfully. The patient was completely relieved of her symptoms post-surgery.

scholarly journals The Role of Aryl-Hydrocarbon Receptor (AhR) in Osteoclast Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2294
Author(s):  
Robin Park ◽  
Shreya Madhavaram ◽  
Jong Dae Ji
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Osteoclast Differentiation ◽  
Environmental Pollutants ◽  
Endogenous Ligand ◽  
Aryl Hydrocarbon ◽  
Binding Time ◽  
Functional Regulation ◽  
Exogenous Ligands ◽  
And Function

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays a crucial role in bone remodeling through altering the interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. While effects of AhR signaling in osteoblasts are well understood, the role and mechanism of AhR signaling in regulating osteoclastogenesis is not widely understood. AhR, when binding with exogenous ligands (environmental pollutants such as polycylic aryl hydrocarbon (PAH), dioxins) or endogenous ligand indoxyl-sulfate (IS), has dual functions that are mediated by the nature of the binding ligand, binding time, and specific pathways of distinct ligands. In this review, AhR is discussed with a focus on (i) the role of AhR in osteoclast differentiation and function and (ii) the mechanisms of AhR signaling in inhibiting or promoting osteoclastogenesis. These findings facilitate an understanding of the role of AhR in the functional regulation of osteoclasts and in osteoclast-induced bone destructive conditions such as rheumatoid arthritis and cancer.

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