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.
Since clinical evidence of hair loss and hair depigmentation following etretinate therapy has been reported, we decided to study the expression levels of several members of the retinoid nuclear receptor superfamily in dermal and epithelial compartments of the human hair follicle. Additionally, we evaluated the effects of several ligands for these receptors on human hair growth in culture in vitro. We observed that the cellular/ cytoplasmic retinoic acid (RA) binding protein-II and the retinoid-X-receptor-alpha were constantly and strongly expressed in both compartments at levels comparable to those of vitamin D receptor. In dermal papilla cells, by contrast with RAR beta which was always expressed, RAR alpha and RAR gamma were not constantly expressed. In dermal sheath fibroblasts, both RAR alpha, RAR beta and RAR gamma mRNAs were moderately expressed, while in the epithelial compartment, namely the plucked hair, we observed the expression of the same genes in the absence of RAR beta. We also observed that RAR agonists all-trans RA and CD367 inhibited the survival of human hair follicles in culture in vitro, while RXR agonist CD2425 stimulated hair growth and survival at levels comparable to those of 1 alpha,25-dihydroxyvitamin D3, suggesting that RXR agonists might stimulate hair growth in humans in vivo.
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