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.

在正常和异常人类毛发生长的生命周期中，硫酸雌酮和肾上腺前体的其他激素分子产生雌二醇的两性二态性。

• 批准号: 323377867
• 负责人: Professor Dr. Ulrich Schweizer, since 8/2021
• 金额: --
• 依托单位: Institut für Biochemie und Molekularbiologie (IBMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/323377867?language=en
• 关键词: Sexually; dimorphic; generation; estradiol; estrone

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.

人类的发根是器官，可以从血液中存在的激素前体自主形成类固醇激素。我们现在在人类毛囊中检测到了两种以前未知的代谢途径。答：硫酸雌酮 (E1S) 形成雌酮 (E1) 和雌二醇 (E2)。它超过雄烯二酮芳构化合成的雌激素数倍。该途径取决于毛发的生长阶段、毛发的身体定位、性别和年龄。 B：由脱氢表雄酮(DHEA)局部形成7α-羟基-脱氢表雄酮(7α-OH DHEA)和雄烯二醇。它们的合成显然受到 E1S 代谢在生长阶段、定位、性别（强烈的两性二态性！）和年龄方面的模拟调节。 E2 调节头发生长。雄烯二醇可以充当雌激素。 7α-OH DHEA 和雄烯二醇在头发中的作用尚不清楚。本项目将探索雄激素性脱发、斑秃和特发性多毛症患者发根中 E1S 和 DHEA 激素代谢物的合成。无论是男性还是女性，过早脱发或体毛过度生长都会带来相当大的心理困扰。孤立的毛根是更大、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，它们适合探索其他类固醇敏感疾病（例如前列腺癌和乳腺癌）中激素合成的内分泌和旁分泌自动调节的基本原理。了解这些基础知识对于所有受男性和女性性激素调节并具有发根等酶供应的器官和组织都很重要。雄激素和雌激素相关疾病（例如前列腺、乳房和骨骼）似乎可能存在常见的病理生理机制。计划中的研究可能会产生与治疗相关的模型。先导化合物的发现是通过筛选类固醇、类固醇抑制剂、生长因子和细胞因子来进行的。