Increased cell volume, accumulation of lipid droplets in the cytoplasm, and nuclear degeneration are phenomena indicating terminal differentiation of human sebocytes followed by holocrine secretion and cell death. The molecular pathways of natural and induced sebocyte elimination are still unknown, however. In this study, SZ95 sebocytes were found to exhibit DNA fragmentation after a 6 h culture followed by increased lactate dehydrogenase release after 24 h, indicating cell damage. With the help of morphologic studies and using Oil Red detection of cellular lipids, cell enlargement, accumulation of lipid droplets in the cytoplasm, and nuclear fragmentation could be observed under treatment with arachidonic acid. Staurosporine, a potent inhibitor of phospholipid Ca2+-dependent protein kinase, increased externalized phosphatidylserine levels on SZ95 sebocytes, detected by annexin V/propidium iodide flow cytometry, as early as after 1 h, whereas dose-dependent reduction of bcl-2 mRNA and protein expression, enhanced DNA fragmentation, and increased caspase 3 levels, detected by caspase 3 inhibitor/propidium iodide flow cytometry, were found after 6 h of treatment. SZ95 sebocyte death was detected as early as after 6 h of SZ95 sebocyte treatment with high staurosporine concentrations (10(-6)-10(-5) M). 5Alpha-dihydrotestosterone (10(-8)-10(-5) M) did not affect externalized phosphatidylserine levels and DNA fragmentation in SZ95 sebocytes but slightly decreased lactate dehydrogenase cell release. Neither acitretin nor 13-cis retinoic acid (10(-8)-10(-5) M) affected externalized phosphatidylserine levels, DNA fragmentation, and lactate dehydrogenase cell release, despite the increased caspase 3 levels under treatment with 13-cis retinoic acid. The combined staurosporine and 13-cis retinoic acid treatment enhanced DNA fragmentation in SZ95 sebocytes to the same magnitude as in cells only treated with staurosporine. In conclusion, SZ95 sebocytes in vitro undergo apoptosis, which can be enhanced by the terminal differentiation inductor arachidonic acid or by staurosporine and leads to cell death. 5Alpha-dihydrotestosterone inhibits SZ95 sebocyte death without involving apoptotic pathways, and retinoids did not affect the programmed death of human sebocytes. The latter result fits well with the currently reported inability of normal skin cells to undergo apoptosis after treatment with retinoids, in contrast to their malignant counterparts.

The penetration of topically applied compounds varies considerably in the different regions of the human body. The presence of hair follicles significantly contributes to this effect by an increase in surface area and a disruption of the epidermal barrier towards the lower parts of the hair follicle. The human hair follicle, hereby, serves not only as a reservoir, but also as a major entry point for topically applied compounds. Topical delivery of active compounds to specific targets within the skin may help reduce side-effects caused by unspecific reactions, and may help develop new strategies in the prevention and treatment of skin diseases. Various drug carrier and drug delivery systems are currently being investigated. The aim of these investigational efforts is to direct topically applied compounds to the different types of hair follicles and, ideally, to specific compartments and cell populations within the hair follicles. Follicular targeting offers opportunities for new developments, not only in hair therapy and in the treatment of hair follicle associated diseases but also in gene therapy and immunotherapy.

Pathogenetic mechanisms in androgenetic alopecia are not yet fully understood; however, it is commonly accepted that androgens like testosterone (T) and 5α-dihydrotestosterone (5α-DHT) inhibit hair follicle activity with early induction of the catagen. Thus, we investigated the influence of T and 5α-DHT on proliferation, cell death and bcl-2/bax expression in cultured dermal papilla cells (DPC) from nonbalding scalp regions of healthy volunteers. T and 5α-DHT induced apoptosis in DPC in a dose-dependent and time-related manner; in addition a necrotic effect due to T at 10^–5M was found. Interestingly, bcl-2 protein expression was decreased in T- and 5α-DHT-treated cells, leading to an increase in the bax/bcl-2 ratio. In addition, T and 5α-DHT induced proteolytic cleavage of caspase 8 and inhibited proliferation of DPC at 10^–5M. High concentrations of T and 5α-DHT were needed to induce apoptotic effects in DPC. These data suggest that DPC from nonbalding scalp regions do have the capacity to undergo apoptosis, but need a high androgen stimulus. The present study provides an interesting new pathogenetic approach in androgenetic alopecia.

Despite the variations of length and type of hair (vellus or terminal), the growth of human hair in all body sites is cyclic. Phases of active hair growth, or anagen, are separated by periods of quiescence, or telogen. The duration of both phases varies greatly depending on the body site. Whether hairs are in anagen/telogen at the time of hair removal is important because only anagen hairs are particularly sensible to physical insults. Photo-epilation is a technique for long-term removal of unwanted hair by thermal destruction of the hair follicle and its reproductive system (stems cells). As melanin is the main chromophor existing in hair follicles the corresponding wavelength spectrum would range from ultraviolet up to infrared light. Furthermore longer wavelengths are preferred as the cromophor lies deep in the skin and the penetration of light is increasing with the wavelength. Thus, in the range of 600-1100 nm melanin absorption may be used for selective photothermolysis of hair follicles. Yet to be resolved questions for permanent destruction are the location of the key follicular target and the possible influence of the hair growth cycle on photothermolysis-induced hair removal. An overview on the individual physiology of the hair follicle is given to discuss the latest strategies for photo-epilation.