Aromatase belongs to the group of cytochrome P450 enzymes () and mediates the aromatization of androgens to estrogens.
Gene
In humans, 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
promoters that are in turn controlled by
hormones,
cytokines, and other factors. The principal action of the enzyme transforms
androstenedione 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,
AMH, 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 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.
See also
Aromaticity
References
- Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril 2006;85:1307-18. PMID 16647373
EC 1.14.14 | Cytochrome P450