Sexually dimorphic generation of estradiol from estrone sulfate and other hormonal molecules from adrenal precursors in the life cycle of normal and abnormal human hair growth.

人的发根是器官，可以从血液中存在的激素前体自动形成类固醇激素。我们现在已经在人类毛囊中检测到两种以前未知的代谢途径。A：从硫酸雌酮（E1 S）形成雌酮（E1）和雌二醇（E2）。它超过了雄烯二酮芳构化的雌激素合成，几倍。这一途径取决于头发的生长阶段、身体位置、性别和年龄。B：由脱氢表雄酮（DHEA）局部形成7 α-羟基-脱氢表雄酮（7 α-OH DHEA）和雄烯二醇。它们的合成明显受到类似于E1 S代谢的调节，如生长期、定位、性别（强烈的两性异形！）和年龄。E2调节头发生长。雄烯二醇可以作为雌激素。7 α-OH DHEA和雄烯二醇在头发中的作用尚不清楚。本研究将探讨雄激素性脱发、斑秃和特发性多毛症患者发根中E1 S和DHEA的激素代谢产物的合成。无论是男性还是女性，头发过早脱落或其他情况，过度的体毛生长都与相当大的心理痛苦有关。孤立的毛根是更大和更重要的重要器官的模型。与其他器官相比，它们相对容易获得。因此，他们是合适的，探索在其他类固醇敏感性疾病，如前列腺癌和乳腺癌的激素合成的内分泌和旁分泌自动调节的基本原则。了解这些基本知识对于所有受男性和女性性激素调节的器官和组织都很重要，并且有一种酶供应，如发根。雄激素和雌激素相关疾病（如前列腺、乳腺和骨骼）的常见病理生理机制似乎是可能的。计划的研究可能会导致与治疗相关的模型。通过筛选类固醇、类固醇抑制剂、生长因子和细胞因子来寻找先导化合物。

Human hair roots are organs and can form autonomously steroid hormones from hormonal precursors present in the blood. We have now detected two previously unknown metabolic pathways in human hair follicles. A: The formation of estrone (E1) and estradiol (E2) from estrone sulfate (E1S). It exceeds the estrogen synthesis by aromatization of androstenedione, several times. This pathway is dependent on the growth phase of the hair, their body localization, sex and age. B: From dehydroepiandrosterone (DHEA) 7alpha-hydroxy-dehydroepiandrosterone (7alpha-OH DHEA) and androstenediol are locally formed. Their synthesis is subject obviously to analog modulations as the E1S metabolism in terms of growth phase, localization, sex (strong sexual dimorphism!) and age. E2 regulates hair growth. Androstenediol can act as estrogen. The roles of 7alpha-OH DHEA and androstenediol in the hair are unknown. In this project the synthesis of hormonal metabolites from E1S and DHEA in hair roots from patients with androgenetic alopecia, alopecia areata and idiopathic hirsutism shall be explored. Both in men and women premature loss of head hair or otherwise, excessive body hair growth are associated with considerable psychological distress. Isolated hair roots are a model for larger and more important vital organs. Compared to other organs, they are relatively easy to obtain. They are therefore suitable, to explore basic principles of intracrine and paracrine autoregulation of hormone synthesis in other steroid-sensitive diseases such as prostate- and breast cancer. Knowing these basics could be important for all organs and tissues that are regulated by male and female sex hormones and have an enzyme supply as hair roots. Common pathophysiologic mechanisms appear possible for androgen and estrogen associated diseases such as the prostate, breast and bone. The planned investigations might lead to models relevant for therapy. Lead finding is intended by screening of steroids, steroid inhibitors, growth factors and cytokines.