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Aromatase belongs to the group of cytochrome P450 enzymes (EC 1.14.14.1 (http://us.expasy.org/cgi-bin/nicezyme.pl?1.14.14.1)) and mediates the aromatization of androgens to estrogens.
Gene
The gene CYP19, located on chromosome 15q21.1, encodes the aromatase enzyme.
Location
The enzyme is located in the endoplasmic reticulum of the cell and its activity is regulated by tissue specific promotors that are in turn controlled by hormones, cytokines, and other factors. The principal action of the enzyme transforms androstendione to estrone and testosterone to estradiol. The aromatase enzyme can be found in many tissues including gonads, brain, adipose tissue, placenta, blood vessels, skin, bone, endometrium as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer.
Activity
Factors known to increase aromatase activity include age, obesity, insulin, gonadotropins, and alcohol. Aromatase activity is decreased by prolactin, MIF, and smoking.
Aromatase activity appears to be enhanced in certain estrogen-dependent local tissue next to breast cancer, 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 and in girls to precocious puberty and macromastia. In both genders, early epiphyseal closure leads to shortness.
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 genders will be tall.
Aromatase inhibitors
The inhibition of the enzyme will lead to profound hypoestrogenism. This may be useful in certain medical conditions where estrogens support the disease process. Thus aromatase inhibitors have become useful in the management of patients with breast cancer whose lesion was found to be estrogen-receptor positive. Investigations are ongoing to look for other applications.
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