Nelly Billoni

Thyroid hormone receptor β1 is expressed in the human hair follicle: THYROID HORMONE RECEPTOR β1 IN HUMAN HAIR

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 TRβ1 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.

Androgenetic alopecia and microinflammation

Today, androgenetic alopecia (AGA) is considered to be an alteration of hair growth and/or a premature aging of the pilosebaceous unit with a multifactorial and even polygenic etiology.1 The fact that the success rate of treatment with either antihypertensive agents, or modulators of androgen metabolism, barely exceeds 30% means that other pathways may be envisioned. The implication of various activators of inflammation in the etiology of AGA has progressively and recently emerged from several independent studies.2–11 A fibroplasia of the dermal sheath, which surrounds the hair follicle, is now suspected to be a common terminal process resulting in theminiaturization and involution of the pilosebaceous unit in AGA.2–8 We review here several observations underlining the possible implication of a slow, silent, and painless process in AGA. Because we think that it should not be confused with a classical inflammatory process, we have called it microinflammation. An early study referred to an inflammatory infiltrate of mononuclear cells and lymphocytes in about 50% of the scalp samples studied.2 Another more recent study by Jaworsky et al.3 confirmed an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles from transitional regions of alopecia (i.e. which are characterized by actively progressing alopecia). This study also reported the occurrence of a developing fibrosis of the perifollicular sheath, together with the degranulation of follicular adventitial mast cells. The miniaturization of the hair follicles was found to be associated with a deposit of so-called ‘‘collagen or connective tissue streamers’’ beneath the follicle,2,7 as well as a 2–2.5 times enlargement of the follicular dermal sheath composed of densely packed collagen bundles.3 This thickening of the dermal sheath in progression zones of AGA has also recently been observed in our laboratory using immunohistochemical staining (Fig. 1). Horizontal section studies of scalp biopsies indicate that the so-called perifollicular fibrosis is generally mild, consisting of loose, concentric layers of fibrotic collagen that must be distinguished from cicatricial alopecia.4 It is unclear whether or not the fibrosis seen in follicular streamers (stelae or fibrous tracts) is permanent and/or alters the downgrowth of anagen hair follicles. Only 55% of male pattern AGA patients with microinflammation had hair regrowth in response to minoxidil treatment, which was less than the 77% of patients with no signs of inflammation,4 suggesting that, to some extent, perifollicular microinflammation may account for some cases of male pattern AGA which do not respond to minoxidil.4 Another study on 412 patients (193 men and 219 women) confirmed the presence of a significant degree of inflammation and fibrosis in at least 37% of AGA cases.5 The upper location of the infiltrate near the infrainfundibulum2–7 clearly distinguishes AGA from alopecia areata (AA), the latter disease being characterized by infiltrates in the bulb and dermal papilla zone.12 The aim of this review is to determine the location and chronology of the microinflammation process within the complex pathophysiology of the human pilosebaceous unit in order to improve the possible approaches for the reduction or prevention of the development of AGA.

Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPARα involvement in hair growth

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.

Pro-Inflammatory Cytokine Cascade in Human Plucked Hair

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 rece