It is well-documented that SREBPs control lipid biosynthesis, PPARc regulates inflammatory responses, and PGC1a controls energy homeostasis. Thus, the results provide evidence that 25HCDS is a potent regulator, which plays an important role in maintenance of hepatic lipid homeostasis and inflammatory responses. The estrogen receptor protein is a member of the superfamily of nuclear receptors whose natural ligand is the hormone 17b-estradiol. Estrogen receptors are present in all vertebrates, highlighting the importance of the ER signal pathway. Binding of 17b-estradiol to ER activates a signaling pathway that regulates several key biological processes such as reproduction, embryonic development and homeostasis. There are two distinct estrogen receptor genes, resulting in two subtypes of estrogen receptors that differ in tissue distribution and ligand preference. In addition to the classical ER ligand inducible transcription activity, there are mounting evidence that ER can act as extra-nuclear activator, independent of gene expression and protein synthesis. These activities are linked to the ERs residing in, or near, the plasma membrane and seem to be involved in breast cancer development and progression. ER is composed by three structural Doxorubicin 25316-40-9 domains: a modulating domain with ligand-independent transactivation function, a DNAbinding domain and a ligand binding domain. The amino acid sequences of the LBD of estrogen receptors from several species are available and they indicate that the core of this domain is highly conserved from mammals to fish Even if sequence homology in the ligand binding domain is high, several studies indicate that estrogenic compounds may have different affinities for ER subtypes and for different organisms. Besides the natural hormone ligands, a large variety of chemical compounds can bind to ERs. Many EDCs have been shown to be toxic for animals and humans due to their ability to interfere with the normal function of ER, leading to many adverse effects such as reproductive problems, several types of cancer and feminization in some fish and amphibians. Thousands of EDCs, belonging to various chemical classes such as drugs, pesticides, byproducts of plastic and healthcare industries, are commonly present in the environment as a result of industrial, agricultural and household waste. EDCs may also arise from the degradation pathway of otherwise harmless compounds. They are of particular concern due to their wide environmental dispersion and to their tendency to bio-accumulate.