The conversion of androstenedione (ANDST) to estrone (E1) is catalysed by aromatase (CYP19A1) associated with the endoplasmic reticulum membrane (Toda et al. 1990, Simpson et al. 1994).
CYP19A1 (aromatase) is the enzyme that catalyses a key aromatization step in the synthesis of estrogens from androgens. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase (Brodie et al. 1981). Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone. In postmenopausal women, estrogen is primarily derived from the aromatization of adrenally-produced androgens into estrogens by CYP19A1. Aromatase inhibitors are a class of drugs used in the treatment of breast cancer in postmenopausal women by competitively inhibiting CYP19A1. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing growth of hormone receptor-positive breast tumours (Chumsri et al. 2011). Aromatase inhibitors can be first-generation (e.g. aminoglutethimide) (Greco et al. 2005), second-generation (e.g. fadrozole) (Browne et al. 1991), and third-generation (e.g. anastrozole, letrozole, and exemestane) (Bhatnagar et al. 1990, Cohen et al. 2002, Buzdar et al. 2002) agents. They can also be divided into type I and type II inhibitors. Type I inhibitors have a steroidal structure similar to androgens and inactivate CYP19A1 irreversibly by blocking the substrate-binding site, and are therefore known as aromatase inactivators. Type II inhibitors are nonsteroidal and their action is reversible.
Aromatase (CYP19A1) catalyses the conversion of androstenedione (ANDST) to estrone (E1). Defects in CYP19A1 can cause aromatase excess syndrome (AEXS; MIM:139300) and aromatase deficiency (AROD; MIM:613546). Affected individuals cannot synthesise endogenous estrogens. In females the lack of estrogen leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal. Mutations causing AEXS include C437Y, R375C, R365Q and E210K (Ito et al. 1993, Morishima et al. 1995, Carani et al. 1997, Maffei et al. 2004).
Aromatase (CYP19A1) catalyses the conversion of androstenedione (ANDST) to estrone (E1). Defects in CYP19A1 can cause aromatase excess syndrome (AEXS; MIM:139300) and aromatase deficiency (AROD; MIM:613546). Affected individuals cannot synthesise endogenous estrogens. In females the lack of estrogen leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal (Bulun 2014).