CYP19

CYP19, officially CYP19A1 in humans, encodes aromatase, a member of the cytochrome P450 superfamily of enzymes. Aromatase catalyzes the aromatization of androgens to estrogens, converting testosterone to estradiol and androstenedione to estrone, a crucial step in estrogen biosynthesis in multiple tissues.

Aromatase is a membrane-bound enzyme located in the endoplasmic reticulum. It requires NADPH and cytochrome P450 reductase for activity. Expression is regulated by tissue-specific promoters producing different transcript variants; primary sites include ovarian granulosa cells, adipose tissue, placenta, and certain brain regions. Placental aromatase is essential for fetal and placental estrogen supply during pregnancy.

Clinical significance: Mutations in CYP19A1 can cause aromatase deficiency, with impaired estrogen production leading to virilization and ambiguous genitalia in 46,XX individuals and disruptions to puberty and secondary sexual development in other contexts. Aromatase excess syndrome results from increased promoter activity or gene duplication, causing elevated estrogen production. Pharmacological inhibition of aromatase using aromatase inhibitors reduces estrogen synthesis and is a standard therapy for estrogen receptor–positive breast cancer and other estrogen-dependent conditions.

Genetics and context: CYP19A1 is located on chromosome 15q21.2 in humans. The gene’s multiple promoters and alternative transcripts underlie tissue-specific regulation, allowing differential expression across tissues and developmental stages. Polymorphisms in regulatory regions can influence aromatase activity, estrogen levels, bone density, and disease risk, making CYP19A1 a focus of studies on reproduction, metabolism, and cancer.