Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into estrogens. The enzyme aromatase can be found in many tissues including gonads (granulosa cells), brain, adipose tissue, placenta, blood vessels, skin, and bone, as well as in tissue of endometriosis, uterine fibroids, breast cancer, and endometrial cancer. It is an important factor in sexual development. 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. Androstenedione + 3O2 + 3NADPH + 3H+ Estrone + Formate + 4H2O + 3NADP+ Testosterone + 3O2 + 3NADPH + 3H+ 17β-estradiol + Formate + 4H2O + 3NADP+ Expression Aromatase is expressed in the gonads, placenta, brain, adipose tissue, bone, and other tissues. It is almost undetectable in adult human liver. Genomics The gene expresses two transcript variants. In humans, the gene CYP19, located on chromosome 15q21.1, encodes aromatase. The gene has nine coding exons and a number of alternative non-coding first exons that regulate tissue specific expression. 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 Aromatase activity is increased by age, obesity, insulin, gonadotropins, and alcohol. It also appears to be enhanced in certain estrogen-dependent local tissue next to breast tissue, endometrial cancer, endometriosis, and uterine fibroids. Aromatase activity is decreased or antagonized by prolactin, anti-Müllerian hormone and glyphosate. Role in sex-determination Aromatase is generally highly present during the differentiation of ovaries. It is also susceptible to environmental influences, particularly temperature. In species with temperature-dependent sex determination, aromatase is expressed in higher