RetinoidThe retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout the body including roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes. Research is also being done into their ability to treat skin cancers.
Selective glucocorticoid receptor modulatorSelective glucocorticoid receptor modulators (SEGRMs) and selective glucocorticoid receptor agonists (SEGRAs) formerly known as dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of the desirable anti-inflammatory, immunosuppressive, or anticancer properties of classical glucocorticoid drugs but with fewer side effects such as skin atrophy. Although preclinical evidence on SEGRAMs’ anti-inflammatory effects are culminating, currently, the efficacy of these SEGRAMs on cancer are largely unknown.
Glucocorticoid receptorThe glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, and immune response. Because the receptor gene is expressed in several forms, it has many different (pleiotropic) effects in different parts of the body. When glucocorticoids bind to GR, its primary mechanism of action is the regulation of gene transcription.
TransrepressionIn the field of molecular biology, transrepression is a process whereby one protein represses (i.e., inhibits) the activity of a second protein through a protein-protein interaction. Since this repression occurs between two different protein molecules (intermolecular), it is referred to as a trans-acting process. The protein that is repressed is usually a transcription factor whose function is to up-regulate (i.e., increase) the rate of gene transcription. Hence the net result of transrepression is down regulation of gene transcription.
Transcription coregulatorIn molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription.
Estrogen receptor alphaEstrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1 (EStrogen Receptor 1). The estrogen receptor (ER) is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription.
Liver X receptorThe liver X receptor (LXR) is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors (LXRs) are important regulators of cholesterol, fatty acid, and glucose homeostasis. LXRs were earlier classified as orphan nuclear receptors, however, upon discovery of endogenous oxysterols as ligands they were subsequently deorphanized. Two isoforms of LXR have been identified and are referred to as LXRα and LXRβ.
Estrogen receptorEstrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs) (GPER (GPR30), ER-X, and Gq-mER), which are mostly G protein-coupled receptors. This article refers to the former (ER).
Vitamin DVitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). The major natural source of the vitamin is synthesis of cholecalciferol in the lower layers of epidermis of the skin, through a photo-chemical reaction of UVB light, from the sun exposure (specifically UVB radiation) or UVB lamps.
Thyroid hormone receptorThe thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response. There are four domains that are present in all TRs. Two of these, the DNA-binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements( HREs).
Histone deacetylaseHistone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. HDAC's action is opposite to that of histone acetyltransferase. HDAC proteins are now also called lysine deacetylases (KDAC), to describe their function rather than their target, which also includes non-histone proteins.
Histone acetyltransferaseHistone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression. In general, histone acetylation is linked to transcriptional activation and associated with euchromatin.
Histone acetylation and deacetylationHistone acetylation and deacetylation are the processes by which the lysine residues within the N-terminal tail protruding from the histone core of the nucleosome are acetylated and deacetylated as part of gene regulation. Histone acetylation and deacetylation are essential parts of gene regulation. These reactions are typically catalysed by enzymes with "histone acetyltransferase" (HAT) or "histone deacetylase" (HDAC) activity. Acetylation is the process where an acetyl functional group is transferred from one molecule (in this case, acetyl coenzyme A) to another.
Hepatocyte nuclear factorsHepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes and transporters involved with glucose, cholesterol, and fatty acid transport and metabolism. As the name suggests, hepatocyte nuclear factors are expressed predominantly in the liver. However HNFs are also expressed and play important roles in a number of other tissues so that the name hepatocyte nuclear factor is somewhat misleading.
Selective androgen receptor modulatorSelective Androgen Receptor Modulators or SARMs are a class of androgen receptor ligands that were developed with the intention of maintaining some of the desirable effects of androgens, such as preventing osteoporosis and muscle loss while reducing risks of undesirable conditions such as prostate cancer. In the late 1990s, the first nonsteroidal SARM, an analog of bicalutamide, was discovered at Imperial Chemical Industries.
Peroxisome proliferator-activated receptorIn the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.
EstriolEstriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost undetectable. However, during pregnancy, estriol is synthesized in very high quantities by the placenta and is the most produced estrogen in the body by far, although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of metabolism and excretion.
GlucocorticoidGlucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau (glucose + cortex + steroid) and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure (see structure below).
Steroid hormoneA steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence cortico-) and sex steroids (typically made in the gonads or placenta). Within those two classes are five types according to the receptors to which they bind: glucocorticoids and mineralocorticoids (both corticosteroids) and androgens, estrogens, and progestogens (sex steroids). Vitamin D derivatives are a sixth closely related hormone system with homologous receptors.
EicosanoidEicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules.
