Steroid sulfatase in the human hair follicle concentrates in the dermal papilla.
5 alpha-dihydrotestosterone is known to play a crucial part in the regulation of hair growth and in the development of androgenetic alopecia. 5 alpha-dihydrotestosterone is formed locally within the hair follicle from the systemic precursor testosterone by cutaneous steroid 5 alpha-reductase. Moreover, adrenal steroids such as dehydroepiandrosterone are converted to 5 alpha-dihydrotestosterone by isolated hair follicles, which may provide an additional source of intrafollicular 5 alpha-dihydrotestosterone levels. Elevated urinary dehydroepiandrosterone and serum dehydroepiandrosterone sulfate have been reported to be present in balding young men. These reports suggest that dehydroepiandrosterone sulfate may act as an important endocrine factor in the development of androgenetic alopecia. Hence the question arises whether the dehydroepiandrosterone sulfate can be metabolized within the hair follicles to yield dehydroepiandrosterone by the microsomal enzyme steroid sulfatase, and where steroid sulfatase might be localized. We therefore performed immunostaining for steroid sulfatase on human scalp biopsies as well as analysis of steroid sulfatase enzyme activity in defined compartments of human beard and occipital hair follicles ex vivo. Using both methods steroid sulfatase was primarily detected in the dermal papilla. Steroid sulfatase activity was inhibited by estrone-3-O-sulfamate, a specific inhibitor of steroid sulfatase, in a concentration-dependent way. Furthermore, we show that dermal papillae are able to utilize dehydroepiandrosterone sulfate to produce 5 alpha-dihydrotestosterone, which lends further support to the hypothesis that dehydroepiandrosterone sulfate contributes to androgenetic alopecia and that steroid sulfatase inhibitors could be novel drugs to treat androgen-dependent disorders of the hair follicle such as androgenetic alopecia or hirsutism.
Hoffmann
R
R
Philipp University, Department of Dermatology, Marburg, Germany. rolf.hoffmann@mailer.uni-marburg.de
Rot
A
A
Niiyama
S
S
Billich
A
A
D000328:Adult; D000505:Alopecia / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D001192:Arylsulfatases / Q000032:analysis / Q000378:metabolism*; D019314:Dehydroepiandrosterone Sulfate / Q000493:pharmacokinetics; D013196:Dihydrotestosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D018859:Hair Follicle / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D043266:Steryl-Sulfatase; D014316:Tritium
D000728:Androgens; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D014316:Tritium; C088768:estrone-3-O-sulfamate; D004970:Estrone; D019314:Dehydroepiandrosterone Sulfate; D001192:Arylsulfatases; D043266:Steryl-Sulfatase