Abstract
Much of the early work on Nuclear Hormone Receptors (NHRs) focused on their essential roles as mediators of sex steroid hormone signaling in reproductive development and function, and thyroid hormone-dependent formation of the central nervous system. However, as NHRs display tissue-specific distributions and activities, it is not surprising that they are involved and vital in numerous aspects of human development and essential for homeostasis of all organ systems. Much attention has recently been focused on the role of NHRs in energy balance, metabolism, and lipid homeostasis. Dysregulation of NHR function has been implicated in numerous pathologies including cancers, metabolic obesity and syndrome, Type II diabetes mellitus, cardiovascular disease, hyperlipidemia, male and female infertility and other reproductive disorders. This review will discuss the dysregulation of NHR function by environmental endocrine disrupting chemicals (EDCs), and the associated pathological consequences of exposure in numerous tissues and organ systems, as revealed by experimental, clinical, and epidemiological studies.
Highlights
This review presents current knowledge concerning the molecular mechanisms of endocrine disrupting chemicals (EDCs) on Nuclear Hormone Receptors (NHRs)
Activation of GPER1 by estradiol results in stimulation of adenylyl cyclase, the release of membrane-tethered epidermal growth factor (EGF), and a cascade of intracellular events that result in hormone responses which are rapid compared with those occurring from classical genomic NHR signaling [37]
What do (1) altered fetal reproductive development, (2) decreased semen quality, and (3) testicular germ cell cancer (TGCC) have in common? In 2001, Skakkeback and colleagues coined this triad of abnormalities ‘Testicular Dysgenesis Syndrome’ (TDS), and proposed that the 3 maladies share a common etiology by which environmental chemicals and genetics result in abnormal development of the fetal testis [112]
Summary
The biological actions of steroids, thyroid hormones, retinoids, and other lipophilic hormones are mediated through a family of intracellular receptors termed the nuclear hormone receptor (NHR). NHRs respond to hormones by associating with transcriptional cofactors, and the receptor–cofactor complexes bind DNA at specific recognition sequences in the regulatory region of target genes. From these sites, the receptors interact with the basic transcriptional apparatus to alter (induce or repress) gene expression. Type I receptors, including the receptors for estrogens (ER-alpha and ER-beta), androgens (AR), progestins (PR), glucocorticoids (GR) and mineralocorticoids (MR), may reside in the cytoplasm or nucleus These receptors respond to activating ligands by undergoing conformational changes that result in loss of associated heat-shock proteins, homo- or heterodimerization, and translocation to chromatin-containing regions of the nucleus. In the unliganded form, these receptors are capable of recruiting corepressors and repressing basal target gene transcription
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
