Aromatase research and its clinical significance.
Aromatase is a member of the cytochrome P450 superfamily that catalyzes the conversion of androgens (C(19)), namely testosterone and androstenedione, into oestrogens (C(18)), oestradiol, and oestrone, respectively. The enzyme is active in various tissues in both females and males, thus oestrogens are produced not only in gonads but also in extra-gonadal localizations such as brain, adipose tissue, breast, skin, and bone. Aromatase gene CYP19A1 located on chromosome 15 comprises nine coding exons and a number of alternative non-coding first exons that regulate tissue-specific expression. Studies on local regulation of aromatase expression and activity are important for understanding processes such as growth of oestrogen-dependent breast cancer. Rare clinical conditions of aromatase deficiency and excess have revealed some new and unexpected oestrogen functions in metabolism and bone health in both women and men. They were further studied using transgenic animal models such as aromatase knockout mice (ArKO) or (AROM+) mice overexpressing human aromatase. Research on aromatase was important for its practical outcome as it contributed to the development of aromatase inhibitors (AIs), an effective and safe group of drugs for the first-line endocrine therapy of breast cancer. Further studies are needed to establish AIs application in other oestrogen-dependent conditions, to overcome the resistance in breast cancer patients, and to develop tissue-specific selective inhibitors. (Pol J Endocrinol 2010; 61 (1): 126-134).
Czajka-Oraniec
Izabella
I
Department of Endocrinology, Medical Centre for Postgraduate Education, Warszawa, Poland.
Simpson
Evan R
ER
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001842:Bone and Bones / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology; D004967:Estrogens / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D011110:Polymorphism, Genetic
D047072:Aromatase Inhibitors; D004967:Estrogens; D001141:Aromatase