So far, the predisposing genes for androgenetic alopecia are unknown and the paradoxical relation between the molecular steps involved in androgen-dependent beard growth and androgen-dependent scalp hair loss is still unclear. However, androgenetic alopecia can be defined as a dihydrotestosterone (DHT) – dependent process with continuous miniaturization (conversion of terminal hairs to vellus hairs) of sensitive hair follicles.
Aromatase inhibitor CYP19
With the progress made in unveiling the intricacies of hair biology, it is evident that there are many more steroidogenic enzymes involved in the onset and development of pattern hair loss. Androgens, because of their interconversion to estrogens, indirectly control estrogen receptor-estrogen binding. Since not all women with female pattern hair loss have hyperandrogenemia or respond to antiandrogen or 5 alpha – reductase inhibitor treatment, researchers have found it important to explore the role of estrogens as another potential factor in pattern hair loss.
Cytochrome P-45 alpha0 aromatase (P45 alpha0arom) is the key enzyme for estrogen biosynthesis. Aromatase is located in estrogen-producing cells in the adrenal glands, ovaries, placenta, testicles, adipose (fat) tissue, and brain. P45 alpha0arom catalyzes the conversion of testosterone to estradiol, of androstenedione to estrone, and of 16 -hydroxylated dehydroepiandrosterone to estriol. In theory, these pathways may diminish the amount of intrafollicular testosterone available for conversion to DHT.
Young women have much higher levels of Cytochrome P-45 alpha0 aromatase in frontal follicles than men, and hair biologists believe the female scalp may have two-fivefold greater amounts of aromatase versus male scalp. This, they believe, may also explain why women may have a sparing of the frontal hairline in androgenetic alopecia, and also why they have a less severe pattern of hair loss than men. An interesting observation made during studies was that women taking aromatase inhibitors tend to develop androgenetic alopecia rather rapidly, indicating a role of aromatase in the pathogenesis of this form of hair loss.
In order to unravel the pathways of estradiol-mediated effects on the hair follicles, studies were conducted to measure aromatase activity in isolated intact human occipital hair follicles by incubating hair follicles. Aromatase was found to be expressed mainly within the root sheaths of the hair follicle. However, some cells of the stalk region of the dermal papilla also stained for aromatase.
The autosomal gene encoding aromatase CYP19 was studied in cases and controls, but no differences were detected, which is why researchers assume that it is unlikely that the aromatase gene is involved in determining pre-disposition to alopecia. It is yet unclear if the estrogens formed from aromatase are responsible for suppressing the severity of hair loss, or whether aromatase is primarily reducing the overall load of androgens formed locally in the hair follicle. In fact, the role of estrogen in female pattern hair loss is still enigmatic.