F7  STEROID SULFATASE IS PRIMARILY EXPRESSED WITHIN THE DERMAL PAPILLA OF HUMAN HAIR FOLLICLES – A NEW PHARMACEUTICAL TARGET FOR THE TREATMENT OF ANDROGENETIC ALOPECIA?

¹Niiyama S., ²Rot A., ²Billich A., ¹Hoffmann R. ¹Dept. of Dermatology, Philipp University, Marburg, Germany; ²Novartis Research Institute Vienna, Wien, Austria.

Dihydrotestosterone (DHT) is known to play a crucial role in the regulation of hair growth and in the development of androgenetic alopecia (AGA). DHT can be formed locally within the hair follicle (HF) from the systemic precursor testosterone by cutaneous steroid 5a-reductase (5aR). In addition, adrenal steroids, such as dehydroepiandrosterone (DHEA), can be converted to DHT by isolated HF as well, which might provide an additional source of DHT. Sulfated DHEA (DHEAS) is the most abundant circulating steroid and elevated urinary DHEA and serum DHEAS has been reported in balding young men. These reports suggest that DHEAS may act as an important endocrine factor in the development of AGA. The question arises whether the DHEAS can be cleaved within the HF to yield DHEA by the microsomal enzyme steroid sulfatase (STS) and where STS is localized within the HF. Therefore we performed immunohistochemistry for STS on human scalp biopsies as well as analysis of STS enzyme activity in defined compartments of occipital human anagen HF ex vivo by HPLC. With both methods STS was mainly detected in the dermal papilla (DP). STS activity was inhibited by estrone-3-O-sulfamate, a specific inhibitor of STS, in a concentration dependent manner (>80 % of inhibition at 1 nM). In sum, we describe for the first time that the DP of the HF appears to be a major site of STS expression in occipital human HF, the site where type 2 5aR activity is concentrated and where androgen receptors are found. It is therefore conceivable that DHEAS can be utilized by the HF to produce DHT which lends further justification to the hypothesis that DHEAS contributes to AGA and that STS inhibitors could be novel drugs to treat androgen dependent disorders such as AGA or hirsutism.