Estrogen receptors, comprised of ERα and ERβ isoforms in mammals, act as ligandmodulated
transcription factors and orchestrate a plethora of cellular functions from sexual development
and reproduction to metabolic homeostasis. Herein, I revisit the structural basis of the binding of
ERα to DNA and estradiol in light of the recent discoveries and emerging trends in the field of nuclear
receptors. A particular emphasis of this review is on the chemical and structural diversity of an everincreasing
repertoire of physiological, environmental and synthetic ligands of estrogen receptors that
ultimately modulate their interactions with cognate DNA located within the promoters of estrogenresponsive
genes. In particular, modulation of estrogen receptors by small molecule ligands represents an important therapeutic
goal toward the treatment of a wide variety of human pathologies including breast cancer, cardiovascular disease,
osteoporosis and obesity. Collectively, this article provides an overview of a wide array of small organic and inorganic
molecules that can fine-tune the physiological function of estrogen receptors, thereby bearing a direct impact on human
health and disease.
Keywords: Endoestrogens, Estrogen receptors, Metalloestrogens, Phytoestrogens, SERMs, Xenoestrogens.
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