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.

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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.