雄激素性脱发的假设发病机制模型:阐明双氢睾酮悖论和速率限制恢复因素。

PubMed ID
G H
发表日期 2018年Feb月

原始出处 医学假说
Medical hypotheses
作者 English  Robert S 

文献标题 雄激素性脱发的假设发病机制模型:阐明双氢睾酮悖论和速率限制恢复因素。
A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors.
A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors.

文献摘要

雄激素性脱发,也称为脱发,是一种慢性进行性疾病,影响80%的男性和50%的女性一生。但是,尽管雄激素性脱发的发病率和广泛的研究,一个连贯的病理模型描述雄激素性脱发的前体,生物步骤过程和生理反应尚不存在。虽然共识是雄激素性脱发是遗传和雄激素介导的双氢睾酮,问题仍然是关于双氢睾酮的确切作用,雄激素性脱发的发病。是什么导致双氢睾酮增加雄激素性脱发易感组织?双氢睾酮通过哪些机制使易发生雄激素性脱发的毛囊小型化?为什么双氢睾酮也与第二身体和面部毛发的生长有关?为什么阉割(雄激素分泌减少95%)能阻止脱发,但不能完全逆转脱发?双氢睾酮与雄激素性脱发同时观察到的组织重塑有关系吗?我们回顾了支持和质疑双氢睾酮与雄激素性脱发因果关系的证据,然后提出了一个基于证据的发病机制模型,试图回答上述问题,解释额外怀疑的雄激素性脱发介质,确定速率限制恢复因素,阐明更好的治疗靶点。该假说认为:(1)慢性头皮张力从帽状腱膜传导,引起雄激素性脱发易感组织的炎症反应(2) 双氢睾酮增加雄激素性脱发易感组织作为炎症反应的一部分;双氢睾酮不能直接使毛囊缩小。相反,双氢睾酮是组织真皮鞘增厚、滤泡周围纤维化和钙化的共同介质,这三种慢性进展性疾病伴随着雄激素性脱发的进展。这些条件重塑雄激素性脱发易发组织-限制卵泡生长空间,氧气和营养供应-导致缓慢,持久的毛囊小型化特征雄激素性脱发。如果是真的,这个假设模型解释了双氢睾酮使雄激素性脱发易感毛囊小型化的机制,描述了雄激素性脱发进展和模式的基本原理,解释了双氢睾酮在脱发和毛发生长中的矛盾作用,并确定了进一步提高雄激素性脱发恢复率的靶点:纤维化、钙化和慢性头皮紧张。


Androgenic alopecia, also known as pattern hair loss, is a chronic progressive condition that affects 80% of men and 50% of women throughout a lifetime. But despite its prevalence and extensive study, a coherent pathology model describing androgenic alopecia's precursors, biological step-processes, and physiological responses does not yet exist. While consensus is that androgenic alopecia is genetic and androgen-mediated by dihydrotestosterone, questions remain regarding dihydrotestosterone's exact role in androgenic alopecia onset. What causes dihydrotestosterone to increase in androgenic alopecia-prone tissues? By which mechanisms does dihydrotestosterone miniaturize androgenic alopecia-prone hair follicles? Why is dihydrotestosterone also associated with hair growth in secondary body and facial hair? Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not fully reverse it? Is there a relationship between dihydrotestosterone and tissue remodeling observed alongside androgenic alopecia onset? We review evidence supporting and challenging dihydrotestosterone's causal relationship with androgenic alopecia, then propose an evidence-based pathogenesis model that attempts to answer the above questions, account for additionally-suspected androgenic alopecia mediators, identify rate-limiting recovery factors, and elucidate better treatment targets. The hypothesis argues that: (1) chronic scalp tension transmitted from the galea aponeurotica induces an inflammatory response in androgenic alopecia-prone tissues; (2) dihydrotestosterone increases in androgenic alopecia-prone tissues as part of this inflammatory response; and (3) dihydrotestosterone does not directly miniaturize hair follicles. Rather, dihydrotestosterone is a co-mediator of tissue dermal sheath thickening, perifollicular fibrosis, and calcification - three chronic, progressive conditions concomitant with androgenic alopecia progression. These conditions remodel androgenic alopecia-prone tissues - restricting follicle growth space, oxygen, and nutrient supply - leading to the slow, persistent hair follicle miniaturization characterized in androgenic alopecia. If true, this hypothetical model explains the mechanisms by which dihydrotestosterone miniaturizes androgenic alopecia-prone hair follicles, describes a rationale for androgenic alopecia progression and patterning, makes sense of dihydrotestosterone's paradoxical role in hair loss and hair growth, and identifies targets to further improve androgenic alopecia recovery rates: fibrosis, calcification, and chronic scalp tension.

Androgenic alopecia, also known as pattern hair loss, is a chronic progressive condition that affects 80% of men and 50% of women throughout a lifetime. But despite its prevalence and extensive study, a coherent pathology model describing androgenic alopecia's precursors, biological step-processes, and physiological responses does not yet exist. While consensus is that androgenic alopecia is genetic and androgen-mediated by dihydrotestosterone, questions remain regarding dihydrotestosterone's exact role in androgenic alopecia onset. What causes dihydrotestosterone to increase in androgenic alopecia-prone tissues? By which mechanisms does dihydrotestosterone miniaturize androgenic alopecia-prone hair follicles? Why is dihydrotestosterone also associated with hair growth in secondary body and facial hair? Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not fully reverse it? Is there a relationship between dihydrotestosterone and tissue remodeling observed alongside androgenic alopecia onset? We review evidence supporting and challenging dihydrotestosterone's causal relationship with androgenic alopecia, then propose an evidence-based pathogenesis model that attempts to answer the above questions, account for additionally-suspected androgenic alopecia mediators, identify rate-limiting recovery factors, and elucidate better treatment targets. The hypothesis argues that: (1) chronic scalp tension transmitted from the galea aponeurotica induces an inflammatory response in androgenic alopecia-prone tissues; (2) dihydrotestosterone increases in androgenic alopecia-prone tissues as part of this inflammatory response; and (3) dihydrotestosterone does not directly miniaturize hair follicles. Rather, dihydrotestosterone is a co-mediator of tissue dermal sheath thickening, perifollicular fibrosis, and calcification - three chronic, progressive conditions concomitant with androgenic alopecia progression. These conditions remodel androgenic alopecia-prone tissues - restricting follicle growth space, oxygen, and nutrient supply - leading to the slow, persistent hair follicle miniaturization characterized in androgenic alopecia. If true, this hypothetical model explains the mechanisms by which dihydrotestosterone miniaturizes androgenic alopecia-prone hair follicles, describes a rationale for androgenic alopecia progression and patterning, makes sense of dihydrotestosterone's paradoxical role in hair loss and hair growth, and identifies targets to further improve androgenic alopecia recovery rates: fibrosis, calcification, and chronic scalp tension.


获取全文 10.1016/j.mehy.2017.12.027