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Med Hypotheses 2002 Nov;59(5):522-6
The hydraulic influence in androgen-related hair growth: implications in autoimmune disease.
Androgen-related changes in hair growth represent something of a mystery. Through the action of dihydrotestosterone (DHT), hair growth is increased in specific areas of the body. Elevated levels of DHT produce a general increase over the larger part of the body, often accompanied by hair loss in specific areas of the scalp. Because of this 'opposite' effect, a genetic difference in the hair follicles is proposed. This view is supported through the success of the 'plug graft' transplantation technique. However, this is unsatisfactory, because transplantation procedures that should work well according to this theory, ultimately fail. There is an alternative 'mechanism', that demonstrates its origins in the prime function of hair as an insulator. This simple mechanism makes sense of all the recognized effects of DHT in the dermal system, and throughout the body. In DHT-related hair growth it can be directly observed. The implication is that DHT achieves its effects through a primary physiological action that can be easily tested given the necessary expertise. Given existing knowledge, such a proven action of DHT would have serious implications for further understanding of female susceptibility to autoimmune disease.
J Dermatol 2002 Jul;29(7):414-8
Effect of two consecutive earthquakes on outbreaks of alopecia areata.
The pathogenesis of alopecia areata (AA) is still unknown. We investigated whether two consecutive earthquakes in Duzce, Turkey within a 3-month interval could precipitate AA. Patients who developed AA after the first earthquake in Duzce were included in this study. The admittance rate and demographic characteristics of AA patients admitted in the same period of the previous year (BE=before earthquake group) were compared to that of AA patients admitted after the earthquake (AE=after earthquake group). The admittance rate and onset of AA after the first earthquake were investigated retrospectively. In addition, possible relationships between the earthquake and age at the first attack, severity of the disease, and ophiasis were studied. The ratio of AA patients in the BE group was 12/1,121 (0.9%), while this value was 26/1,430 (1.8%) in the AE group (p=0.07). There were no significant differences with regard to sex, age of the first attack, severity of the disease, or ophiasis between the two groups. AA appeared between 18-28 weeks after the first earthquake in 14 (53.8%) of the patients. The earthquake did not increase the admittance rate of AA significantly. This finding suggests that a stressful event such a natural disaster is not a unique factor in AA outbreaks.
J Invest Dermatol 2001 Dec;117(6):1342-8
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.
J Invest Dermatol 2002 Feb;118(2):335-7
Interleukin-1 receptor antagonist allele 2 and familial alopecia areata.
Alopecia areata affects 1%-2% of the population and is hypothesized to be an autoimmune, organ specific T-cell mediated reaction directed against the human hair follicle. It is characterized by loss of hair in patches (alopecia areata) with progression in some individuals to total loss of scalp hair (alopecia totalis) or to loss of all scalp and body hair (alopecia universalis). The interleukin-1 receptor antagonist (IL-1RN) gene was found to be associated with more severe clinical outcome in several chronic inflammatory diseases, including alopecia areata. The IL-1RN*2 allele was found to be associated with alopecia areata severity in a British case-control study. In this paper, we analyzed alopecia areata probands in a family-based sample (n = 131 parent-offspring trios) to study the association between alleles of the IL-1RN and various phenotypes of alopecia areata. In considering all patients with any form of alopecia areata, no association was found with IL-1RN. IL-1RN*2 allele was not associated with alopecia totalis and alopecia universalis. A borderline association was observed between IL-1RN and patchy alopecia areata but it was not statistically significant (p =0.06). We also observed an association between IL1-RN*1 allele and patchy alopecia areata (p =0.045).
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