No abstract

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.

Peroxisome proliferator-activated receptors (PPARs), which belong to the nuclear hormone receptor superfamily, have recently been described as potent key regulators of epidermal development. As 1,25-dihydroxyvitamin D3, retinoic acid and triiodothyronine are known to exert effects on skin and hair follicle growth through similar receptors, we decided to investigate both the expression pattern of the PPAR alpha, -delta and -gamma subtypes and their role in human hair follicles. Using reverse transcriptase-polymerase chain reaction and immunohistochemistry, we established that PPAR alpha, -delta and -gamma were expressed in both dermal and epithelial human hair follicle cells. Additionally, we evaluated the dose effect of clofibrate, a PPAR alpha ligand, on the survival of human hair follicles in culture. A beneficial effect was observed within a narrow range of concentrations.

It has been previously reported that minoxidil inhibits the activity of lysyl hydroxylase (LH), an enzyme which catalyzes the formation of hydroxylysine, which is necessary for proper maturation of collagen at the transcriptional and enzymatic levels. Using the reverse transcriptase-polymerase chain reaction, we confirmed that this inhibition occurred at least at the transcriptional level. Furthermore, we took advantage of this sensitive and rapid method to perform a quantitative structure activity relation study using several compounds structurally related to minoxidil. We found that when the C6 of the pyrimidinyl moiety was substituted, it had to be by a tertiary nitrogen, i.e. an N-piperidin ring for the inhibition of LH mRNA synthesis to be observed. Surprisingly, however, we found that 2,4-diamino-pyrimidin-3-oxide, a new compound lacking an organic moiety para to the nitroxide oxygen, also retained a high inhibitory effect on LH mRNA expression, comparable to that of minoxidil. We thus conclude that the presence of a substituent para to the nitroxide oxygen is dispensable for inhibition of LH mRNA to be observed in vitro. This brings new insights into the design of therapeutic agents useful in any condition where an overproduction of mature collagen is unwanted, i.e. accelerated wound healing, keloids and localized scleroderma.