Role of Nuclear Receptors in Controlling Erythropoiesis

Abstract

Nuclear receptors (NRs), are a wide family of ligand-regulated transcription factors sharing a common modular structure composed by an N-terminal domain and a ligand-binding domain connected by a short hinge linker to a DNA-binding domain. NRs are involved in many physiological processes, including metabolism, reproduction and development. Most of them respond to small lipophilic ligands, such as steroids, retinoids, and phospholipids, which act as conformational switches. Some NRs are still “orphan” and the search for their ligands is still ongoing. Upon DNA binding, NRs can act both as transcriptional activators or repressors of their target genes. Theoretically, the possibility to modulate NRs activity with small molecules makes them ideal therapeutic targets, although the complexity of their signaling makes drug design challenging. In this review, we discuss the role of NRs in erythropoiesis, in both homeostatic and stress conditions. This knowledge is important in view of modulating red blood cells production in disease conditions, such as anemias, and for the expansion of erythroid cells in culture for research purposes and for reaching the long-term goal of cultured blood for transfusion.

Selenium, Iodine and Iron–Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism

“…This is of high relevance in iron-deficient pregnant women [ 53 ]. However, the interrelationship between Fe and TH is bidirectional as TH directly stimulate erythyropoiesis, predominantly via the TR-alpha receptor [ 54 , 55 ]. Fe supplements and improvement in iron status in areas with endemic deficiency facilitate iodide utilization for TH biosynthesis, as demonstrated in children [ 12 ] as well as for anemic (mainly female) patients [ 56 ].…”

Current investigations for liver fibrosis treatment: between repurposing the FDA-approved drugs and the other emerging approaches

“…They are classified into six subfamilies and comprise a DNA-binding domain (DBD) and a ligand-binding domain (LBD). In the context of liver fibrosis, NRs have been implicated in regulating HSC activation and fibrogenesis [122,123]. In addition to NRs, membrane Receptors expressed by HSCs have also been identified as potential targets for anti-fibrotic therapies.…”

Are sex differences in blood cell count and hemoglobin moderated by the 2D:4D ratio? A cross‐sectional study in a Ghanaian population

“…While testosterone may promote erythropoiesis, estrogen tends to inhibit it. The administration of a high dose of estrogen has been shown to cause anemia in both humans and animals 8 . Estrogen has been demonstrated to play a protective role against erythrocytosis as demonstrated in the lower prevalence of chronic mountain sickness disease or Monge's disease among premenopausal but not menopausal women 9 .…”

“…9 Estrogen protects against erythrocytosis by repressing GATA1, leading to erythroid progenitor cell apoptosis via a direct ligand-dependent protein-protein interactions. 8 The Organizational Hypothesis posits that prenatal testosterone (PT) exposure leads to sexual dimorphism in human phenotypic traits including the second-to-fourth digit ratio (2D:4D). 10 The 2D:4D is the putative marker of PT exposure.…”