Nuclear Hormone Receptors and Their Ligands: Metabolites in Control of Transcription

Abstract

Nuclear hormone receptors are a family of transcription factors regulated by small molecules derived from the endogenous metabolism or diet. There are forty-eight nuclear hormone receptors in the human genome, twenty of which are still orphans. In this review, we make a brief historical journey from the first observations by Berthold in 1849 to the era of orphan receptors that began with the sequencing of the Caenorhabditis elegans genome in 1998. We discuss the evolution of nuclear hormone receptors and the putative ancestral ligands as well as how the ligand universe has expanded over time. This leads us to define four classes of metabolites—fatty acids, terpenoids, porphyrins and amino acid derivatives—that generate all known ligands for nuclear hormone receptors. We conclude by discussing the ongoing efforts to identify new classes of ligands for orphan receptors.

Nematode nuclear receptors as integrators of sensory information

“…The enormous structural diversity of potential NHR ligands, and their connection to nutrient signals, is already greatly appreciated. 26,27 These approaches have the potential to yield novel strategies for the control of parasitic nematodes, which continue to represent a major impediment to human and livestock health as well as crop production.…”

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors—An In Silico Screening Study

“…The other, very important group of the NHR receptors that may be affected by EDCs are alpha and beta thyroid hormone receptors (TRs). Thyroid hormones are synthesized from tyrosine; hence, they are the amino acid derivatives [ 30 ]. The amino acids sequences of TRα and TRβ are identical in 85%, and both show high homology across species [ 31 ].…”

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver

“…These nuclear receptors (NRs) are activated by lipophilic compounds, including hormones, which can diffuse from producing cells into target cells, including liver cells, close to or at a distance of the hormone production sites in the body. These activators comprise steroids, retinoids, thyroid hormones, vitamin D3, fatty acids, and fatty acid derivatives, all known as potent regulators of cell differentiation, development, and organ physiology [ 12 ]. Notably, the activity of these receptors can also be modulated by posttranslational modifications, including phosphorylation, acetylation, SUMOylation, and ubiquitination [ 13 , 14 ].…”