Aromatase

Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily (EC 1.14.14.1), which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into estrogens. The aromatase enzyme can be found in many tissues including gonads, brain, adipose tissue, placenta, blood vessels, skin, bone, and endometrium, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer. It is an important factor in sexual development. Some bodybuilders taking steroids also take antiaromatase supplements to prevent excess testosterone conversion into estrogens, which can cause gynecomastia.

Function

Aromatase is localized in the endoplasmic reticulum 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 to estrone and testosterone to estradiol). These steps include three successive hydroxylations of the 19-methyl group of androgens, followed by simultaneous elimination of the methyl group as formate and aromatization of the A-ring (see Figure).

Genomics

The gene expresses two transcript variants.^[3] In humans, the gene CYP19, located on chromosome 15q21.1, encodes the aromatase enzyme.^[4] CYP19 is present in an early-diverging chordate, the cephalochordate amphioxus (the Florida lancelet, Branchiostoma floridae), but not in the earlier diverging tunicate Ciona intestinalis. 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, corals). However, estrogens may be synthesized in some of these organisms, via other unknown pathways.

Activity

Factors known to increase aromatase activity include age, obesity, insulin, gonadotropins, smoking and alcohol. Aromatase activity is decreased by prolactin, anti-Müllerian hormone, and zinc. Aromatase activity appears to be enhanced in certain estrogen-dependent local tissue next to breast tissue, endometrial cancer, endometriosis, and uterine fibroids.

Disorders

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, and in girls to precocious puberty and gigantomastia. In both sexes, early epiphyseal closure 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 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 (low estrogen levels). Thus, aromatase inhibitors have become useful in the management of patients with breast cancer whose lesion was found to be estrogen receptor positive. An example of an aromatase inhibitor is letrozole, marketed originally under the name 'Femara.' Aromatase inhibitors are also beginning to be prescribed to men on testosterone replacement therapy 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.^[5]

References

Further reading

External links

• "U.S. study of gay sheep may shed light on sexuality", via WikiNews, 15 August 2005.