A catechol estrogen is a

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal a ...

that contains

catechol Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is a toxic organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amoun ...

(1,2-dihydroxybenzene) within its structure. The catechol estrogens are

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s of

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

and

estrone Estrone (E1), also spelled oestrone, 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 estriol. Estrone, as well as the other estrogens, are synthesized ...

and include the following compounds: * 2-Hydroxylated: ** 2-Hydroxyestradiol ** 2-Hydroxyestrone ** 2-Hydroxyestriol * 4-Hydroxylated: ** 4-Hydroxyestradiol ** 4-Hydroxyestrone ** 4-Hydroxyestriol The most abundant catechol estrogen in serum and urine is 2-hydroxyestrone, with 2-hydroxyestradiol and 2-hydroxyestriol also being formed, while the principal 4-hydroxy catechol estrogen, 4-hydroxyestrone, is present in only small amounts in urine. 4-Hydroxyestriol has been detected in the urine of

pregnant Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

women. The catechol estrogens are formed from estradiol and estrone by

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

s predominantly in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

but also in extrahepatic tissues, and are

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

by catechol O-methyltransferase (COMT) into

methoxy In organic chemistry, a methoxy group is the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula . On a benzene ring, the Hammett equation classifies a methoxy substituent at the ''para'' position ...

lated estrogens such as

2-methoxyestradiol 2-Methoxyestradiol (2-ME2, 2-MeO-E2) is a natural metabolite of estradiol and 2-hydroxyestradiol (2-OHE2). It is specifically the 2- methyl ether of 2-hydroxyestradiol. 2-Methoxyestradiol prevents the formation of new blood vessels that tumors ...

and 4-methoxyestrone as well as by

conjugation Conjugation or conjugate may refer to: Linguistics *Grammatical conjugation, the modification of a verb from its basic form * Emotive conjugation or Russell's conjugation, the use of loaded language Mathematics *Complex conjugation, the change ...

via other phase II enzymes. Under poor conditions of inactivation by phase II enzymes, catechol estrogens can undergo

oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

to reactive

quinone The quinones are a class of organic compounds that are formally "derived from aromatic compounds benzene.html" ;"title="uch as benzene">uch as benzene or naphthalene] by conversion of an even number of –CH= groups into –C(=O)– groups with ...

s and semiquinones, and this has been hypothesized to contribute to estrogen-induced

carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...

. Similarly to estradiol and estrone, catechol estrogens possess estrogenic activity. 2-Hydroxylated catechol estrogens are weak and possibly

antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or i ...

ic estrogens, whereas their 4-hydroxylated counterparts are more potent in their estrogenic activity. For instance, 2-hydroxyestrone reportedly shows negligible uterotrophic effect in animals, whereas 4-hydroxy catechol estrogens show moderate changes in stimulating uterine weight. In addition to being

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (locomotion), the surface over which an organism lo ...

s for COMT similarly to

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol ( benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a ...

s like

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 8 ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

, and

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

, catechol estrogens are potent

competitive Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indi ...

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s of COMT as well as of

tyrosine hydroxylase Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine, L-tyrosine to L-DOPA, L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as ...

, and may affect both catecholamine biosynthesis and metabolism.

References

{{Monoamine metabolism modulators Catechol-O-methyltransferase inhibitors Estranes Estrogens Human metabolites Steroid hormones

See also

References