Im going to cut and paste for the guys:
Quote:
Classical concepts
Obstruction of the pilosebaceous follicle canal occurs in the infrainfundibulum [1, 13]. This is due to anomalies of proliferation, adhesion and differentiation of keratinocytes which do not separate from each other and so obstruct the canal lumen, leading to the formation of a micro-comedo. This initial acneiform lesion, generally invisible clinically, is present in 28% of biopsies of apparently normal skin in patients with acne [14].
The sebaceous gland continues to produce sebum which cannot be evacuated, leading to dilation of the pilosebaceous follicle and hence to a clinically visible lesion, the “comedo” [1, 13].
Recent data
Role of hormones
Keratinocytes in the infrainfundibulum, as well as sebocytes, are also targets for androgens. Keratinocytes in the pilosebaceous canal possess androgen receptors and the enzyme system required to metabolize androgens [4].
– 5α reductase type I predominates in keratinocytes in the infrainfundibulum of the pilosebaceous canal [3] whereas 5α reductase type II is predominant in normal epidermis.– In vitro, it has been shown that the combined activity of 5α reductase type I and 17β hydroxysteroid dehydrogenase is two to seven times greater in keratinocytes in the infrainfundibulum than in those in other parts of the epidermis [15].This suggests that anomalies in androgen metabolism in keratinocytes in the infrainfundibulum could lead to anomalies in proliferation and differentiation of these cells (hyperkeratinization and an immuno response perhaps? B). Local hormonal phenomena would also contribute to formation of the micro-comedo.
These data reinforce the notion that acne is related to sensitivity to “peripheral” androgens. More recently, it has been shown that both keratinocytes and sebocytes have the enzymes necessary for the transformatation of cholesterol into dehydroepiandrosterone. Thus skin may be considered as a steroidogenesis organ [16].
Role of cytokines
In vitro, addition of interleukin-1α to culture medium containing a human pilosebaceous canal [17, 18] led to the formation of micro-comedos. This effect may be inhibited by antagonists of interleukin-1α which block the receptor, confirming the specificity of the phenomenon. Interleukin-1α is secreted by keratinocytes in the epidermis and infrainfundibulum, notably in reaction to local irritation.
This could explain the frequency of open and closed comedos of the chin (area rubbed with the fingers) and around the scalp (rubbed by hair, irritation from hair gels). Likewise, the irritation induced by some hygiene or cosmetic products could help in the formation of new micro-comedos and be a factor in maintaining acne.
Hyperproliferation of keratinocytes
Ex vivo, keratinocytes of the pilosebaceous canal have a higher proliferation index (marking with Ki 67), in subjects with acne compared to healthy control subjects. This increased proliferation index is found in the affected area and apparently healthy acne skin[/b](In androgenic alopecia too? B) [19]. These results justify treatment of the entire surface of the acneiform zone whether or not there are visible lesions.
Role of adhesive molecules
Integrins are adhesive molecules that ensure cohesion between keratinocytes. They notably act on regulation of the proliferation and migration of keratinocytes [20, 21]. Recent studies have shown modifications in expression of integrins α2, α3, α5 in keratinocytes in the infrainfundibulum of acne follicles [22]. Changes in expression of integrins could also play a role in the formation of the micro-comedo.
Role of sebum composition
Hyperseborrhea decreases the concentration of linoleic acid in sebum by dilution (see above). This low linoleic acid content could induce an anomaly of keratinocyte differentiation in the infrainfundibulum affecting formation of the micro-comedo [1]. A recent double-blind study [23] against placebo compared the effects of a topical treatment containing linoleic acid on acne lesions. After one month, the size of the comedos had significantly decreased in zones receiving linoleic acid. Free fatty acids, which have been shown to be produced in the sebaceous gland, could also affect keratinocyte differentiation [11].
Thus, formation of micro-comedo, the initial acne lesion, could be the result of several anomalies of the infrainfundibular keratinocyte and its environment: production of interleukin-1, abnormal expression of keratinocyte integrins, anomalies of intra keratinocyte metabolism of androgens and anomalies in the composition of sebum.
Third step: Formation of inflammatory lesions
Classical concepts
Histology studies have shown that right at the start of the formation of a comedo, T lymphocytes are present around the pilosebaceous follicle [24, 25]. Subsequently, P. Acnes plays a central role in the inflammatory phenomena associated with acne [1]. This Gram positive anaerobe proliferates in the comedo. It contains lipases that split sebum triglycerides into glycerol and free fatty acids. Free fatty acids and other fragments of P. acnes diffuse across the comedo wall, leading to an afflux of polynuclear neutrophils by chemotaxis [26]. Polynuclear neutrophils produce enzymes in the perifollicular tissue, notably metalloproteases, which cause rupture of the pilosebaceous follicle wall [27] with diffusion of inflammation in the deep layers. The inflammatory reaction is amplified by reaction to foreign bodies (many macrophages and giant cells) [1, 26, 27].
The classical actors in inflammation become involved-prostaglandins, leucotrienes, macrophages, complement. Today, this is leading to the development of a therapeutic approach via 5 lipoxygenase inhibitors [28].
We have been wondering WHY the immune system attacks in androgenic alopecia and why the first inflammation might be stuck at the infidulum (the opening in the dermis where the hair comes out onto the skin). Perhaps, and just perhaps…too much keratinization (hyperkeratinization) happens due to alpha five reductase TYPE one along with too much sebum being secreted, making it difficult for some of the dead keratinocyte cells to get the hell out of the body…inducing the immune system to attack. I cannot figure out for the life of me why the inflammation in AGA is usually restricted to the very top of the follicle and not the whole damned thing, but perhpas its like acne is from an inflammatory standpoint…
I had no clue androgen receptors were around the keratinocytes and alpha five reductase TYPE ONE was present there and not type 2. Perhaps we need to inhibit both of them?
Anybody got any ideas?