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To understand better the mechanisms by which thyroid hormone can exert its effects on the hair follicle, we looked for the expression of members of the thyroid hormone receptor (TR) family in human hair follicles. Immunoreactive TRs were detected in both dermal and epithelial compartments of the human pilosebaceous unit. Using reverse transcriptase-polymerase chain reaction, we established that TRbeta1 was the predominant form of TR expressed in the human hair follicle. In addition, we investigated the effects of 3,3', 5-triiodo-L-thyronine (T3) on the survival of human hair follicles in vitro, to understand the role of this thyroid hormone on hair follicle homeostasis. A physiological level of free T3 significantly enhanced human hair survival in vitro.

Using reverse transcriptase polymerase chain reaction we showed that freshly plucked human anagen hair expressed both type 1 (80 kD) and type 2 (60 kD) interleukin (IL)-1 receptor mRNAs. The IL-1 receptor type 1 was functional since after in vitro stimulation of plucked hair with IL-1Α, we observed the induction of mRNA(s) for the inflammatory cytokines IL-1Β, tumour necrosis factor Α and IL-6 as well as for the chemokines monocyte chemotactic and activating factor and IL-8. In addition, the growth of dissected human anagen hairs in culture in vitro was significantly and dose-depen-dently inhibited by IL-1Α as a consequence of hair bulb degradation. These observations, together with those of other authors in IL-1Α transgenic mice evidence the inhibitory role of IL-1 on human hair growth. Therefore, in order to identify individuals with high inflammatory potential in their hair follicle environment, we designed a rapid and simple assay to detect variations in the level of IL-1Α production in the overnight supernatant of plucked hairs in culture. We observed that 32.7% of the specimens from the volunteers tested (n = 116) could be considered highly inflammatory in terms of IL-1Α production. Altogether, these results suggest that in alopecia androgenetica, hair growth might be negatively influenced by IL-1, directly produced by the outer root sheath keratinocytes. Consequently, identifying the ‘inflammatory alopecic individual’ might be of clinical interest to discriminate among individuals for whom anti-IL-1 strategies might be of therapeutic relevance.

Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen consumption and PGE2 production. This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.

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In order to define the respective involvement of steroidogenesis enzymes subtypes in the control of hair follicle homeostasis, we evaluated, by semiquantitative RT/PCR, the expression levels of mRNAs coding for 17 β-hydroxysteroid dehydrogenase type 1 and type 2, 3β-hydroxysteroid dehydrogenase, Cyt.P450-aromatase, steroid 5α-reductase type 1 and type 2 and 11 β-hydroxysteroid dehydrogenase. These assays were performed for several components of the pilosebaceous unit (PSU); fresh plucked anagen hairs, sebaceous glands and primary culture of dermal papilla, as well as other tissues involved in an active steroid metabolism (human testis, liver, placenta, prostate, ovary, uterus and adrenals) as controls. We found that plucked hair (i.e. mainly keratinocytes from the inner and outer root sheaths) expressed: (1) very high levels of 17β-hydroxysteroid dehydrogenase type 2 corresponding to levels found in liver and placenta; (2) high levels of steroid 5-α-reductase type 1 corresponding to levels found in testis, liver and ovary, and moderate levels of 17 β-hydroxysteroid dehydrogenase type 1, which corresponded to the expression in testis, prostate and uterus. In contrast, Cyt.P450-aromatase, 3β-hydroxysteroid dehydrogenase and steroid 5α-reductase type 2 were poorly expressed in the pilosebaceous unit as compared with other tissues. Interestingly, expression patterns of these enzymes in primary cultures of dermal papilla were distinctive since 5α-reductase type 1 and 11 β-hydroxysteroid dehydrogenase were the only mRNA detected. Taken together, these results suggest that not only sebaceous gland but also outer root sheath keratinocytes may contribute, through the activity of the steroid 5α-reductase type 1, to the pathogenesis of androgen-dependent alopecia.