What is the Aryl Hydrocarbon Receptor?

The Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor protein that belongs to the basic helix-loop-helix (bHLH) Per-Arnt-Sim (PAS) family of transcription factors. It was originally characterized as the dioxin or polycyclic aromatic hydrocarbon receptor due to the role it plays in detoxifying a variety of environmental pollutants. That was until extensive research identified several groups of endogenous ligands and AhR’s function in biological development and homeostasis was discovered. This intracellular receptor is widely expressed in human tissues and has diverse physiological roles, including the regulation of immune system development, cell proliferation, and differentiation.

Nuclear Receptors

Nuclear receptors are a family of ligand-regulated transcription factors with important physiological functions. These receptors are located in the cytoplasm or the nucleus of the cell. Nuclear receptors are classified as transcription factors due to their ability to bind directly to DNA and regulate the expression of adjacent genes. They are a class of proteins responsible for sensing steroids, hormones, vitamins, and certain other molecules. By modulating the expression of specific genes involved in various cellular functions, these transcription factors mediate the effects of small molecule drugs, hormones, and other xenobiotics. They play an important role in embryonic development and adult homeostasis while influencing a wide variety of functions including fatty acid metabolism and detoxification of foreign substances. 

What is Environmental Toxicology?

Environmental toxicology is a multidisciplinary field of science that focuses on studying the effects of manmade and natural chemical, biological, and physical agents on living organisms in their natural habitats. Environmental toxicology employs risk assessment principles where the potential toxicity of a chemical is examined relative to exposure of the target population. Environmental toxicologists work in academia, government agencies, and industry. They apply principles of chemical fate and transport in the environment, epidemiology and species differences to evaluate potential toxic impacts on ecosystems and human health. An important part of this evaluation is understanding the dose-response relationship for a toxicologic effect relative to exposure to that chemical.

Nuclear receptors and the Microbiome: Does the road to happiness go through the gut?

The microbiome or microbiota are the terms used for the microbes that live on and inside the human body. Trillions of microorganisms make up the microbiome including bacteria, fungi, parasites, and viruses. It is estimated that there are more microbial cells than human cells in the body and the majority of these microbes reside in the gut. There is a growing amount of research that has recently changed our understanding of the microbiome from being just a collection of symbiotic organisms to actively participating in a bidirectional communication system called the gut-brain axis.

Pharmacotherapy is based on the interplay of pharmacokinetics and pharmacodynamics, which allows scientists to understand the effect drugs have on the human body and helps researchers develop drugs that are safe and effective. These two concepts explain how the body impacts drugs (pharmacokinetics) and how those drugs can then impact the body (pharmacodynamics).

What is the Nuclear Receptor Superfamily?

The nuclear receptor superfamily is a group of intracellular transcription factors that directly regulate gene expression in response to lipophilic molecules. These receptors are found in metazoan organisms such as nematodes, insects, and vertebrates. Nuclear receptors affect a wide variety of physiologic functions including development, reproduction, and metabolism and are associated with diseases such as Alzheimer’s, cancer, and diabetes.

Learn about developing a testing strategy for EDCs in water (and how INDIGO can help)

INDIGO Biosciences cell-based reporter assays have been used in environmental research on water for years due to their ease of use. Our CSO Jack Vanden Heuvel has even done his own research in this field utilizing INDIGO kits. (Take a look at the posters “Environmental and human health impacts of spreading oil and gas wastewater on roads” and “Detection and removal of biologically active organic micropollutants from hospital wastewater.”) Using in vitro receptor transactivation assays like those produced by INDIGO Biosciences is a crucial step to improve monitoring of our water systems and decrease the risk posed by complex mixtures of chemicals in the environment. Reporter assays can detect the cumulative toxicity posed by mixtures of known and unknown chemicals found in a sample. Cell-based nuclear receptor specific reporter assays such as INDIGO’s estrogen receptor assays, androgen receptor assays, and thyroid receptor assays can screen for endocrine-like activity in water samples that can cause adverse health effects to humans and the environment.

Environmental Monitoring for Endocrine Disrupting Chemicals [and the importance of utilizing bioassays]

Endocrine disrupting chemicals (EDCs) are a class of pollutants that has garnered a lot of attention. These are specific chemicals that disrupt or interfere with elements of endocrine signaling, a critical system that controls metabolism, growth, tissue, reproduction, mood, and other factors and functions in the human body. Depending on the type and outcome, EDCs can impact puberty, immune function, stress, weight, bone health, and more. Some common examples of sources of EDCs are:

Endocrine Disrupting Chemicals and Environmental Toxicology

Environmental toxicology is a multidisciplinary field of science concerned with the study of the harmful effects of various chemical, biological, and physical agents on living organisms. Environmental toxicologists study the effects of toxicants at various concentrations in labs and try to understand the potential for the bioaccumulation in food webs, including our own food supply. Harmful effects of chemicals like DDT and pollutants, insecticides, pesticides, and fertilizers have been found to affect organisms and their communities by reducing species diversity and abundance. These changes in population dynamics then affect the ecosystem by reducing its productivity and stability.

The assessment of a drug candidate’s cross-activity with human xenobiotic-sensing receptors provides important early indications of that drug’s potential for downstream drug-drug interactions or other toxicology concerns. Prior to moving into human trials, preclinical studies utilize animals as human surrogates to assess a drug’s pharmacokinetic and toxicologic profiles. A wide range of animal models are used in preclinical studies for drug discovery including mice, rats, dogs, zebrafish, rabbits, and non-human primates. In research, these animals are used because they are orthologs. Orthologs are animals of different species that share genes that evolved from a common ancestor and have retained a similar function to those genes in humans.