So I guess years and years of evidence that dht is the main culprit behind Androgenetic Alopecia is completely wrong. This is broscience at its finest! Please tell me more about imagination land.
DHT triggers everything, Fibrosis and collagen built up are just the end results. There is a reason why PGD2 is overly expressed which is a sign of local chronic inflammation.
http://www.hairlosstalk.com/interac...w-Dermaroller-Study-Thoughts-comments/page224
Cellular and molecular mechanisms of chronic inflammation-associated organ fibrosis
Satoshi Ueha[SUP]1,2[/SUP],
Francis H. W. Shand[SUP]1,3[/SUP] and
Kouji Matsushima[SUP]1,2[/SUP]*
- [SUP]1[/SUP] Department of Molecular Preventive Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
- [SUP]2[/SUP] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Tokyo, Japan
- [SUP]3[/SUP] Department of Pharmacology, University of Melbourne, Melbourne, VIC, Australia
Organ fibrosis is a pathological condition associated with chronic inflammatory diseases.
In fibrosis, excessive deposition of extracellular matrix (ECM) severely impairs tissue architecture and function, eventually resulting in organ failure. This process is mediated primarily by the induction of myofibroblasts, which produce large amounts of collagen I, the main component of the ECM. Accordingly, the origin, developmental pathways, and mechanisms of myofibroblast regulation are attracting increasing attention as potential therapeutic targets. The fibrotic cascade, from initial epithelial damage to eventual myofibroblast induction, is mediated by complex biological processes such as macrophage infiltration, a shift from Th1 to Th2 phenotype, and by inflammatory mediators such as transforming growth factor-β. Here, we review the current understanding of the cellular and molecular mechanisms underlying organ fibrosis.
erifollicular fibrosis: pathogenetic role in androgenetic alopecia.
Yoo HG,
Kim JS,
Lee SR,
Pyo HK,
Moon HI,
Lee JH,
Kwon OS,
Chung JH,
Kim KH,
Eun HC,
Cho KH.
Source
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, and Institute of Dermatological Science, Seoul National University, Seoul, Korea.
Abstract
Androgenetic alopecia (Androgenetic Alopecia) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10(-9)-10(-7) M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10(-8) M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-beta1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-beta1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-beta1 antibody (10 microg/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-beta1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the Androgenetic Alopecia, and the inhibitory effects on T-induced procollagen and TGF-beta1 expression may explain another possible mechanism how finasteride works in Androgenetic Alopecia.
Article: Perifollicular fibrosis: pathogenetic role in androgenetic alopecia.
Source: Biol Pharm Bull. 2006 Jun;29(6):1246-50.
Author(s): Yoo HG, Kim JS, Lee SR, Pyo HK, Moon HI, Lee JH, Kwon OS, Chung JH, Kim KH, Eun HC, Cho KH
Department of Dermatology, Seoul National University College of Medicine, Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, and Institute of Dermatological Science, Seoul National University. |
Summary:
Fibrosis is a scarring process in the skin that can damage the hair follicle (hair loss). This study shows that increased Testosterone speeds up fibrosis while treatment with Finasteride helps slow fibrosis. Stopping or slowing fibrosis may be another method by which Finasteride may help prevent hair loss.
Androgenetic alopecia (Androgenetic Alopecia) is a dihydrotestosterone (DHT)-mediated process, characterized by continuous miniaturization of androgen reactive hair follicles and accompanied by perifollicular fibrosis of follicular units in histological examination. Testosterone (T: 10(-9)-10(-7) M) treatment increased the expression of type I procollagen at mRNA and protein level. Pretreatment of finasteride (10(-8) M) inhibited the T-induced type I procollagen expression at mRNA (40.2%) and protein levels (24.9%). T treatment increased the expression of transforming growth factor-beta 1 (TGF-beta1) at protein levels by 81.9% in the human scalp dermal fibroblasts (DFs). Pretreatment of finasteride decreased the expression of TGF-beta1 protein induced by an average of T (30.4%). The type I procollagen expression after pretreatment of neutralizing TGF-beta1 antibody (10 mug/ml) was inhibited by an average of 54.3%. Our findings suggest that T-induced TGF-beta1 and type I procollagen expression may contribute to the development of perifollicular fibrosis in the Androgenetic Alopecia, and the inhibitory effects on T-induced procollagen and TGF-beta1 expression may explain another possible mechanism how finasteride works in Androgenetic Alopecia.
http://www.derma-haarcenter.ch/files...+Barcelona.pdf
|
Cosmet Dermatol. 2009 Jun;8(2):83-91
Androgenetic alopecia in males: a histopathological and ultrastructural study.
El-Domyati M, Attia S, Saleh F, Abdel-Wahab H.
Department of Dermatology, Faculty of Medicine, Al-Minya University, Al-Minya, Egypt.
Background Androgenetic alopecia is a common cosmetic hair disorder, resulting from interplay of genetic, endocrine, and aging factors leading to a patterned follicular miniaturization. Microinflammation seems to be a potential active player in this process. Aims To study the histopathological and ultrastructural changes occurring in male androgenetic alopecia (Androgenetic Alopecia). Patients/methods Fifty-five subjects were included in this study (40 with Androgenetic Alopecia and 15 as normal age-matched controls). Skin biopsies from frontal bald area and occipital hairy area were subjected to histopathological examination, immunohistochemical staining for collagen I and ultrastructural study. Results The frontal bald area of patients showed highly significant increase in telogen hairs and decrease in anagen/telogen ratio and terminal/vellus hair ratio (P < 0.001). Perifollicular inflammation was almost a constant feature in early cases and showed a significant correlation with perifollicular fibrosis (P = 0.048), which was more marked with thickening of the follicular sheath in advanced cases. Conclusion Follicular microinflammation plays an integral role in the pathogenesis of Androgenetic Alopecia in early cases. Over time, thickening of perifollicular sheath takes place due to increased deposition of collagen, resulting in marked perifollicular fibrosis, and sometimes ends by complete destruction of the affected follicles in advanced cases.
http://www.biomediclaser.com/pdf/Inf...c-Alopecia.pdf
Formation of fibrous tissue or fibroplasia of the dermal sheath, which surrounds the hair follicle, is now suspected to be a common terminal process resulting in the
miniaturization. Involution of the pilosebaceous unit in this form of baldness and sustained microscopic
follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is
considered a possible cofactor in the complex etiology of androgenetic alopecia. However, till date, the
inflammatory component has not been explored in developing treatment protocols for androgenetic
alopecia.
Fibrosing Alopecia in a Pattern DistributionPatterned Lichen Planopilaris or Androgenetic Alopecia With a Lichenoid Tissue Reaction Pattern?
Patients developed progressive fibrosing alopecia of the central scalp, without the multifocal areas of involvement typical of lichen planopilaris and pseudopelade. Perifollicular erythema, follicular keratosis, and loss of follicular orifices were limited to a patterned area of involvement. Biopsy specimens of early lesions demonstrated hair follicle miniaturization and a lichenoid inflammatory infiltrate targeting the upper follicle region. Advanced lesions showed perifollicular lamellar fibrosis and completely fibrosed follicular tracts indistinguishable from end-stage lichen planopilaris, pseudopelade, or follicular degeneration syndrome.
http://archderm.jamanetwork.com/article.aspx?articleid=189906
INFLAMMATORY PHENOMENA AND FIBROSIS
The implication of microscopic follicular inflammation in the pathogenesis of Androgenetic Alopecia has emerged from several independent studies: An early study referred to an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles, associated with an enlargement of the follicular dermal sheath composed of collagen bundles (perifollicular fibrosis), in regions of actively progressing alopecia.[
25] Horizontal section studies of scalp biopsies indicated that the perifollicular fibrosis is generally mild, consisting of loose, concentric layers of collagen that must be distinguished from cicatricial alopecia.[
26] The term 'microinflammation' has been proposed, because the process involves a slow, subtle, and indolent course, in contrast to the inflammatory and destructive process in the classical inflammatory scarring alopecias.[
27] The significance of these findings has remained controversial. However, morphometric studies in patients with male pattern Androgenetic Alopecia treated with minoxidil showed that 55% of those with microinflammation had regrowth in response to treatment, in comparison to 77% in those patients without inflammation and fibrosis.[
26] Moreover, some forms of primary fibrosing alopecia may represent pathological exaggeration of Androgenetic Alopecia associated with follicular inflammation and fibrosis, specifically postmenopausal frontal fibrosing alopecia,[
28] and fibrosing alopecia in a pattern distribution.[
29]
An important question is how the inflammatory reaction pattern is generated around the individual hair follicle. Inflammation is regarded as a multistep process which may start from a primary event. Some authors proposed that alopecia may result from cumulative physiological degeneration of selected hair follicles. They described in healthy murine skin clusters of perifollicular macrophages as perhaps indicating the existence of a physiological program of immunologically controlled hair follicle degeneration by which malfunctioning follicles are removed by programmed organ deletion, and suggested that perhaps an exaggerated form of this process might underlie some forms of primary scarring alopecia.[
30] The observation of a perifollicular infiltrate in the upper follicle near the infundibulum of human hair follicles in Androgenetic Alopecia suggests that the primary causal event for the triggering of inflammation might occur near the infundibulum.[
27] On the basis of this localization and the microbial colonization of the follicular infundibulum with
Propionibacterium sp.,
Staphylococcus sp.,
Malassezia sp., or other members of the transient flora, one could speculate that microbial toxins or antigens could be involved in the generation of the inflammatory response. Alternatively, keratinocytes themselves may respond to oxidative stress from irritants, pollutants, and UV irradiation, by producing nitric oxide, and by releasing intracellularly stored IL-1α. This pro-inflammatory cytokine by itself has been shown to inhibit the growth of isolated hair follicles in culture. [
31] Moreover, adjacent keratinocytes, which express receptors for IL-1, start to engage the transcription of IL-1 responsive genes: mRNA coding for IL-1β, TNFα, and IL-1α, and for specific chemokine genes, such as IL-8, and monocyte chemoattractant protein-1 (MCP-1) and MCP-3, themselves mediators for the recruitment of neutrophils and macrophages, have been shown to be upregulated in the epithelial compartment of the human hair follicle.[
27] Besides, adjacent fibroblasts are also fully equipped to respond to such a pro-inflammatory signal. The upregulation of adhesion molecules for blood-borne cells in the capillary endothelia, together with the chemokine gradient, drives the transendothelial migration of inflammatory cells, which include neutrophils through the action of IL-8, T cells, and Langerhans cells at least in part through the action of MCP-1. After processing of localized antigen, Langerhans cells, or alternatively keratinocytes, which may also have antigen presenting capabilities, could then present antigen to newly infiltrating T lymphocytes and induce T-cell proliferation. The antigens are selectively destroyed by infiltrating macrophages, or natural killer cells. On the occasion that the causal agents persist, sustained inflammation is the result, together with connective tissue remodeling, where collagenases, such as matrix metalloproteinase (also transcriptionally driven by pro-inflammatory cytokines) play an active role.[
27] Collagenases are suspected to contribute to the tissue changes in perifollicular fibrosis.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929555/
http://www.hairlosstalk.com/interac...-Thoughts-comments/page144?highlight=biopsies
