Aromatase is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 responsible for a key step in the biosynthesis

Biosynthesis

Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenase

Monooxygenase

Monooxygenases are enzymes that incorporate one hydroxyl group into substrates in many metabolic pathways. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NADH.-Classification:...

s that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization

Aromaticity

In organic chemistry, Aromaticity is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone. The earliest use of the term was in an article by August...

 of androgen

Androgen

Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...

s into estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

s. The aromatase enzyme can be found in many tissues including gonads, brain

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

, adipose tissue

Adipose tissue

In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...

, placenta

Placenta

The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

, blood vessels, skin

Skin

-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

, bone

Bone

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

, and endometrium

Endometrium

-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...

, as well as in tissue of endometriosis

Endometriosis

Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...

, uterine fibroids

Uterine fibroids

A uterine fibroid is a benign tumor that originates from the smooth muscle layer and the accompanying connective tissue of the uterus.Fibroids are the most common benign tumors in...

, breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, and endometrial cancer

Endometrial cancer

Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...

. It is an important factor in sexual development. Some bodybuilders

Bodybuilding

Bodybuilding is a form of body modification involving intensive muscle hypertrophy. An individual who engages in this activity is referred to as a bodybuilder. In competitive and professional bodybuilding, bodybuilders display their physiques to a panel of judges, who assign points based on their...

 taking steroid

Steroid

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

s also take antiaromatase supplements to prevent excess testosterone

Testosterone

Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 conversion into estrogens, which can cause gynecomastia

Gynecomastia

Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...

.

Function

Aromatase is localized

Subcellular localization

The cells of eukaryotic organisms are elaborately subdivided into functionally distinct membrane bound compartments. Some major constituents of eukaryotic cells are: extracellular space, cytoplasm, nucleus, mitochondria, Golgi apparatus, endoplasmic reticulum , peroxisome, vacuoles, cytoskeleton,...

 in the endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 where it is regulated by tissue-specific promoters that are in turn controlled by hormones, cytokines, and other factors. It catalyzes the last steps of estrogen biosynthesis from androgens (specifically, it transforms androstenedione

Androstenedione

Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...

 to estrone

Estrone

Estrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...

 and testosterone

Testosterone

Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 to estradiol

Estradiol

Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...

). These steps include three successive hydroxylation

Hydroxylation

Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

s of the 19-methyl group of androgens, followed by simultaneous elimination of the methyl group as formate

Formic acid

Formic acid is the simplest carboxylic acid. Its chemical formula is HCOOH or HCO2H. It is an important intermediate in chemical synthesis and occurs naturally, most notably in the venom of bee and ant stings. In fact, its name comes from the Latin word for ant, formica, referring to its early...

 and aromatization of the A-ring (see Figure).

Genomics

The gene expresses two transcript variants. In humans, the gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

 CYP19, located on chromosome

Chromosome

A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...

 15q21.1, encodes the aromatase enzyme. CYP19 is present in an early-diverging chordate

Chordate

Chordates are animals which are either vertebrates or one of several closely related invertebrates. They are united by having, for at least some period of their life cycle, a notochord, a hollow dorsal nerve cord, pharyngeal slits, an endostyle, and a post-anal tail...

, the cephalochordate amphioxus (the Florida lancelet

Lancelet

The lancelets , also known as amphioxus, are the modern representatives of the subphylum Cephalochordata, formerly thought to be the sister group of the craniates. They are usually found buried in sand in shallow parts of temperate or tropical seas. In Asia, they are harvested commercially as food...

, Branchiostoma floridae

Lancelet

The lancelets , also known as amphioxus, are the modern representatives of the subphylum Cephalochordata, formerly thought to be the sister group of the craniates. They are usually found buried in sand in shallow parts of temperate or tropical seas. In Asia, they are harvested commercially as food...

), but not in the earlier diverging tunicate

Tunicate

Tunicates, also known as urochordates, are members of the subphylum Tunicata, previously known as Urochordata, a group of underwater saclike filter feeders with incurrent and excurrent siphons that is classified within the phylum Chordata. While most tunicates live on the ocean floor, others such...

 Ciona intestinalis

Ciona intestinalis

Ciona intestinalis is a urochordata , a tunicate widely distributed in Northern European waters. As an invasive species, it has also spread to other parts of the world....

. Thus, the aromatase gene evolved early in chordate evolution and does not appear to be present in nonchordate invertebrates (e.g. insects, molluscs, echinoderms, sponges

Sea sponge

Sponges are animals of the phylum Porifera . Their bodies consist of jelly-like mesohyl sandwiched between two thin layers of cells. While all animals have unspecialized cells that can transform into specialized cells, sponges are unique in having some specialized cells, but can also have...

, corals). However, estrogens may be synthesized in some of these organisms, via other unknown pathways.

Activity

Factors known to increase aromatase activity include age

Senescence

Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...

, obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

, insulin

Insulin

Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

, gonadotropins, smoking

Tobacco smoking

Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...

 and alcohol

Alcohol

In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

. Aromatase activity is decreased by prolactin

Prolactin

Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...

, anti-Müllerian hormone

Anti-müllerian hormone

Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene. It inhibits the development of the Müllerian ducts in the male embryo. It has also been called Müllerian inhibiting factor , Müllerian-inhibiting hormone , and Müllerian-inhibiting substance...

, and zinc

Zinc

Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...

.
Aromatase activity appears to be enhanced in certain estrogen-dependent local tissue next to breast tissue, endometrial cancer, endometriosis, and uterine fibroids.

Aromatase excess syndrome

A number of investigators have reported on a rather rare syndrome of excess aromatase activity. In boys, it can lead to gynecomastia

Gynecomastia

Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...

, and in girls to precocious puberty

Precocious puberty

As a medical term, precocious puberty describes puberty occurring at an unusually early age. In most of these children, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is...

 and gigantomastia

Gigantomastia

Hypertrophy of the breast is a rare disease of the breast connective tissues; the indication is a breast weight increase that exceeds , which enlargement causes muscular discomfort and over-stretching of the skin envelope, leading to ulceration...

. In both sexes, early epiphyseal closure

Epiphysis

The epiphysis is the rounded end of a long bone, at its joint with adjacent bone. Between the epiphysis and diaphysis lies the metaphysis, including the epiphyseal plate...

 leads to short stature.

Aromatase deficiency syndrome

This syndrome is due to a mutation of gene CYP19 and inherited in an autosomal recessive way. Accumulations of androgens during pregnancy may lead to virilization

Virilization

In biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...

 of a female at birth (males are not affected). Females will have primary amenorrhea. Individuals of both sexes will be tall, as lack of estrogen does not bring the epiphyseal lines to closure.

Aromatase inhibitors

The inhibition of the enzyme leads to profound hypoestrogenism

Hypoestrogenism

Hypoestrogenism refers to a lower than normal level of estrogen, the primary sex hormone for women. In general, lower levels of estrogen may cause differences in the breasts, genitals, urinary tract and skin....

 (low estrogen levels). Thus, aromatase inhibitor

Aromatase inhibitor

Aromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....

s have become useful in the management of patients with breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

 whose lesion was found to be estrogen receptor

Estrogen receptor

Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...

 positive. An example of an aromatase inhibitor is letrozole

Letrozole

Letrozole is an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery.Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme...

, marketed originally under the name 'Femara.' Aromatase inhibitors are also beginning to be prescribed to men on testosterone replacement therapy

Androgen replacement therapy

Androgen replacement therapy is a hormone treatment often prescribed to counter the effects of male Hypogonadism. It is also prescribed to lessen the effects or delay the onset of normal male aging...

 as a way to keep estrogen levels from spiking once doses of testosterone are introduced to their systems.

Extracts of certain (white button variety: Agaricus bisporus) mushrooms have been shown to inhibit aromatase in vitro.

External links

• "U.S. study of gay sheep may shed light on sexuality", via WikiNews
  Wikinews
  Wikinews is a free-content news source wiki and a project of the Wikimedia Foundation. The site works through collaborative journalism. Wikipedia co-founder Jimmy Wales has distinguished Wikinews from Wikipedia by saying "on Wikinews, each story is to be written as a news story as opposed to an...
  
  , 15 August 2005.