How does baldness develop?
Changes begin with focal perivascular basophilic degeneration of the lower third of the connective tissue vagina of the hair follicle located in the anagen phase. Later, at the level of the excretory duct of the sebaceous gland, the perifollicular lymphohistiocytic infiltrate is formed. The destruction of the connective tissue vagina determines the irreversibility of hair loss. Approximately 1/3 of the biopsy specimens are detected by multinucleated giant cells surrounding the fragments of the hair. In the place of the formed bald head, most follicles are short, reduced in size. It should be mentioned that horizontal sections of the biopsy are more convenient for morphometric analysis.
Under the influence of ultraviolet rays in areas devoid of hair protection, degenerative changes in the skin develop.
With the help of modern research methods it is shown that the appearance of baldness is accompanied by a decrease in blood flow. Unlike the richly vascularized normal follicle, the vessels surrounding the root of the hair follicle are small and tortuous, with difficulty. It remains unclear whether the reduction in blood flow is primary or secondary to alopecia. It was suggested that the same factors are responsible for the changes in both vessels and follicles.
In normal hair loss, the anagen phase of the hair cycle is shortened and, accordingly, the amount of hair in the telogen phase is increased, which can be determined from the trichogram in the frontopariet area long before hair loss becomes obvious.
Miniaturization of hair follicles leads to a decrease in the diameter of the hair produced by them, sometimes 10-fold (up to 0.01 mm instead of 0.1 mm), which is more pronounced in women than in men. Some follicles are delayed with entry into the anagen phase after hair loss, the mouth of such follicles look empty.
The pathogenesis of normal alopecia (hair loss)
Currently, the role of androgens in the development of normal alopecia is universally recognized.
The hypothesis of androgenic nature of baldness is quite justified, as it allows to explain a number of clinical observations: the presence of baldness in humans and other primates; the presence of the disease in men and women; combination of baldness in persons of both sexes with seborrhea and acne, and in some women with hirsutism; arrangement of hair loss zones on the scalp.
J. Hamilton showed the absence of baldness in eunuchs and in castrated adult men. The appointment of testosterone caused baldness only in genetically predisposed subjects. After testosterone withdrawal, the progression of alopecia stopped, but hair growth did not resume.
The assumption of hypersecretion of testicular or adrenal androgens in balding men has not been confirmed. Thanks to modern methods of determining free and bound androgens, it has been shown that the normal level of androgens is sufficient for the appearance of baldness in genetically predisposed men.
Women have a different situation; the degree of alopecia depends in part on the level of circulating androgens. Up to 48% of women with diffuse baldness suffer from polycystic ovaries; hair loss on the head in such patients is often combined with seborrhea, acne and hirsutism. The maximum changes in hair growth occur after menopause, when the level of estrogen falls, and "androgen supply" remains. During the menopause, androgens cause hair loss only in genetically predisposed women. With a less pronounced genetic predisposition, baldness develops only with increased production of androgens or medication with androgen-like action (for example, progestrogens as oral contraceptives, anabolic steroids that athletes often take). At the same time, in some women, even a sharp increase in the level of androgens does not cause any significant alopecia, although the manifestation of hirsutism in such cases always occurs.
Since the establishment of the leading role of androgens in the development of normal balding, the efforts of many scientists have been focused on revealing the mechanism of their action. Brilliant results of transplantation of autografts containing hair follicles from the occipital region to the balding zone convincingly showed that each hair follicle possesses a genetic program that determines its response to androgens (androgen-sensitive and androgen-resistant follicles).
The effect of androgens on hair follicles varies in different parts of the body. So, androgens stimulate the growth of the beard, the growth of pubic hair, in the armpits, on the chest and, on the contrary, slow the growth of hair on the head in the area of the androgen-sensitive follicles in genetically predisposed subjects. Hair growth is controlled by different hormones: testosterone (T) stimulates the growth of pubic and axillary hair; dihydrotestosterone (DTS) causes the growth of the beard and the usual hair loss on the scalp.
The emergence of normal baldness is determined by two key factors: the presence of androgen receptors and the activity of androgen-converting enzymes (5-alpha-reductase I and II types, aromatase and 17-hydroxy-steroid dehydrogenase) in various parts of the scalp.
It was found that in the fronto-parietal region in men the level of androgen receptors is 1.5 times higher than in the occipital region. The presence of androgen receptors is demonstrated in the culture of dermal papilla cells taken from the scalp of both balding and non-algal subjects, and is indirectly confirmed by the good effect of antiandrogens in diffuse alopecia in women. In the cells of the matrix and the outer root vagina of the hair follicle, these receptors are not detected.
The second key factor in the pathogenesis of normal alopecia is the change in the balance of enzymes involved in the metabolism of androgens. 5a-reductase catalyzes the process of conversion of T into its more active metabolite - DTS. Although I type 5a-reductase predominates in the extracts of the scalp tissue, type II of this enzyme is also found in the hairy vagina and dermal papilla. Moreover, it is known that individuals with congenital deficiency of type II 5-reductase do not suffer from ordinary baldness. The DTS receptor complex has a high affinity for nuclear chromatin receptors, as a result of their contact, the process of inhibition of hair follicle growth and its gradual miniaturization is included.
While 5a-reductase promotes the conversion of T into DTS, the aromatase enzyme converts androstenedione to estrone and T to estradiol. Thus, both enzymes play a role in the occurrence of normal alopecia.
When studying the metabolism of androgens in the scalp of the scalp, increased activity of 5-reductase in the centers of alopecia was revealed. In men, the activity of 5a-reductase in the skin of the frontal region is 2 times higher than in the occiput; the activity of aromatase in both areas is minimal. In women, the activity of 5a-reductase in the fronto-parietal region is also 2 times higher, but the total amount of this enzyme in women is half that of men. The activity of aromatase in the scalp of the scalp is higher in women than in men. Preservation of the anterior hair line in most women with normal hair loss is probably due to the high activity of aromatase, which converts androgens to estrogens. The latter, as is known, have an antiandrogenic effect due to their ability to increase the level of proteins that bind sex hormones. Intensive hair loss in men is associated with low aromatase activity and. Respectively, with increased TTP production.
Some steroidal enzymes (3alpha, 3beta, 17beta-hydroxydrosteroids) have the ability to convert weak androgens, such as dehydroepiandrosterone. In more powerful androgens, having swap tissue targets. The concentration of these enzymes in the balding and non-sliced areas of the head is the same, but their specific activity in the frontal region is much higher than in the occipital region, and in men compared with women this figure is much larger.
It is also known that the appointment of growth hormone to men with a deficiency of this hormone increases the risk of androgenic alopecia. This effect is explained either by direct stimulation of androgen receptors by an insulin-like growth factor-1, or this factor acts indirectly, activating 5a-reductase and, accordingly, accelerating the conversion of T to TPA. The function of sex hormone binding proteins has been little studied. It has been suggested that a high level of these proteins makes T less accessible to metabolic processes, reducing the risk of baldness.
It is necessary to take into account the influence on the process of alopecia cytokines and growth factors. Accumulating data testify to the important role of regulation of expression of cytokine genes, growth factors and antioxidants during the initialization of the hair cycle. Attempts are being made to identify key molecules of cyclic hair growth activity. It is planned at the subcellular and nuclear level to investigate the changes caused by these substances in their interaction with the cells of the hair follicle.