The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects). Whether acting via direct nuclear effects, indirect non-nuclear actions, or a combination of both, the effects of estrogens on gene expression are controlled by highly regulated complex mechanisms. In this chapter, we summarize the knowledge gained in the past 60 years since the discovery of the estrogen receptors on the mechanisms governing estrogen-mediated gene expression. We provide an overview of estrogen biosynthesis, and we describe the main mechanisms by which the female sex hormone controls gene transcription in different tissues and cell types. Specifically, we address the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1). We also describe mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors. Finally, we discuss natural compounds that are able to target specific estrogen receptors and their implications for human health and medical therapeutics.

Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.