Aromatase

Aromatase is a member of the cytochrome P450 enzyme family (gene CYP19A1) that catalyzes the aromatization of androgens to estrogens, a key step in estrogen biosynthesis. It converts testosterone to estradiol and androstenedione to estrone, enabling local and systemic estrogen production in various tissues. The enzyme operates in the endoplasmic reticulum as a membrane-bound protein and requires electrons from NADPH delivered via P450 oxidoreductase to perform three successive oxygenation steps that restructure the A-ring of the steroid into an aromatic ring.

Expression and regulation of aromatase are governed by tissue-specific promoters, allowing different tissues to regulate estrogen production independently. In the ovary, aromatase is expressed in granulosa cells and is upregulated by follicle-stimulating hormone (FSH). Placental, adipose, brain, bone, and other tissues also express aromatase, contributing to circulating and local estrogen levels. In adipose tissue, inflammatory signals and increased adiposity can raise aromatase activity, linking obesity to higher estrogen production, particularly after menopause.

Clinical and physiological significance includes estrogen-dependent development and maintenance of female secondary sexual characteristics, bone health, and reproductive function. Aromatase deficiency, caused by mutations in CYP19A1, leads to estrogen deficiency with virilization in XX individuals and impaired puberty in affected individuals. Conversely, excess aromatase activity can contribute to elevated estrogen levels in certain conditions. Therapeutically, aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) are used to reduce estrogen production in hormone-sensitive breast cancer and other estrogen-dependent disorders, with side effects including hot flashes and decreased bone density.