Aromatase functions
Aromatase is an enzymatic system responsible for the conversion of androgens, typically male sex hormones, into estrogens, which are instead characteristic of the female organism. As the name itself reminds us, aromatase has the ability to aromatize the first ring of androgen carbon (ring A) through the oxidation and subsequent elimination of a methyl group.
Both estrogens and androgens are found - although in very different concentrations and proportions - in both sexes, where they hold prominent physiological roles. They are therefore typical but not exclusive of one sex over the other.
In mammals all steroid hormones, including androgens and estrogens, are synthesized from cholesterol. Examining the various stages of steroidogenesis we can see how the androgen and estrogen secretion is interdependent; the latter are in fact synthesized from androgens.
Androgens can therefore be considered the estrogen pro-hormones.
The various steps of steroidogenesis are regulated by a series of enzymes, whose concentration and activity is the limiting step of the various biochemical steps. We have already seen how the aromatase enzyme, encoded by the CYP19 gene, is able to perform the conversion of androgens at 19 carbon atoms (androstenedione and testosterone) into estrogens at 18 carbon atoms (in estrone and estradiol, respectively).
Located in the endoplasmic reticulum of the cells in which it is expressed, aromatase is an enzymatic complex consisting of two components: the cytochrome P450 aromatase (aromatase P450) and the flavoprotein (NADPH) cytochrome P450 reductase.
Cytochrome P450 reductase contains the heme group and the steroid binding site; in the presence of molecular oxygen and NADPH, it catalyzes the series of concentrated reactions that lead to the formation of the A-phenolic ring of estrogens, while the NADPH-cytochrome P450 reductase is responsible for the transfer of reducing equivalents from NADPH to cytochrome P450.
For each mole of synthesized androgen 3 moles of O 2 and 3 moles of NADPH are required.
The transcription of the aromatase gene, as well as the expression of the enzyme itself, occurs in a large number of tissues, such as the gonadal (testicles and ovary), endometrial, adipose, muscular, hepatic, cerebral, and piliferous (the aromatase is opposed to hair loss and hair growth), connective and placental.
Aromatase inhibitors
In women of fertile age the ovary is the largest producer of estrogen. In men and post-menopause, on the other hand, these hormones are produced largely from the peripheral conversion of androgens by aromatase. Being an enzyme characteristic of adipose tissue, the lower levels of testosterone in obese men compared to normal weight are put in relation to the greater activity of aromatases. Not surprisingly, high concentrations of estrogen in the male are typically accompanied by a reduction in fertility, gynecomastia and erectile dysfunction. However, too high levels of estrogen are dangerous in women, as this is a known and documented risk factor for numerous forms of breast cancer. Since cancer cells need estrogen for their proliferation, one of the most widespread therapeutic approaches is to deprive them of such support. For this reason, in menopausal women, this result can be achieved through aromatase inhibitor drugs (Anastrozole - Arimidex ®, Letrozolo - Femara ®, Exemestano - Aromasin ®). These medicines are illegally used also in the sports field, especially in body building, to prevent the anabolic steroids taken for doping purpose are quickly converted into estrogen to maintain homeostasis; this conversion is an unwanted event, as it promotes water retention, tends to increase fatty deposits and can cause gynecomastia. Always with the aim of increasing the plasma levels of endogenous, or possibly exogenous, testosterone, aromatase inhibitors can also be used in the prevention and treatment of andropause.
