Topical Estrogen Accelerates Hair Regrowth in Mice After Chemotherapy-Induced Alopecia by Favoring the Dystrophic Catagen Response Pathway to Damage

Estrogen receptor ligands are important modulators of skin physiology and are involved in the control of normal hair follicle cycling. Here, we have studied the effects of topically applied 17-β-estradiol on pathologic hair follicle cycling as seen during chemotherapy-induced alopecia, one of the major unresolved problems of clinical oncology. For this study we employed a well-established murine model that mimics chemotherapy-induced alopecia in humans. For precisely quantifying the area of hair loss and hair regrowth in this model in vivo, we developed a simple planimetric assay (dotmatrix planimetry). We show that topical 17-β-estradiol significantly alters the cycling response of murine follicles to cyclophosphamide, whereas the estrogen antagonist ICI 182.780 exerted no such effects. Initially, topical 17-β-estradiol enhanced chemotherapy-induced alopecia significantly by forcing the follicles into the dystrophic catagen response pathway to hair follicle damage, whereas follicles treated by ICI 182.780 or vehicle shifted into the dystrophic anagen response pathway. Consequently, the regrowth of normally pigmented hair shafts after chemotherapy-induced alopecia was significantly accelerated in the 17-β-estradiol treated group. Our data encourage one to explore topical estrogens as a potential stimulant for hair re-growth after chemotherapy-induced alopecia

Elektronen-Spinpolarisation beim Photoeffekt mit zirkularpolarisiertem Licht an Alkalischichten

Heinzmann U, Jost K, Kessler J, Ohnemus B. Elektronen-Spinpolarisation beim Photoeffekt mit zirkularpolarisiertem Licht an Alkalischichten. Zeitschrift für Physik. 1972;251:354-364.The spin polarization of photoelectrons emitted by alkali surfaces illuminated with monochromatic circularly polarized radiation has been observed. Maximum spin polarization of 4.5% is obtained with cesium at a wavelength of about 4500 A. Both maximum spin polarization and the wavelength of the maximum decrease monotonically with decreasing atomic number. The spin polarization is zero within experimental errors, in the case of solid sodium and lithium

The hair follicle as an estrogen target and source

For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17β-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target.Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders

Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and are strongly hair cycle-dependent. In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes. In telogen follicles, PRL-like immunoreactivity was detected in outer root sheath (ORS) keratinocytes. During early anagen (III to IV), the developing inner root sheath (IRS) and the surrounding ORS were positive for PRL. In later anagen stages, PRL could be detected in the proximal IRS and the inner layer of the ORS. The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS. In early anagen, PRLR immunoreactivity occurred in the distal part of the ORS around the developing IRS, and subsequently to a restricted area of the more distal ORS during later anagen stages and during early catagen. The dermal papilla (DP) stayed negative for both PRL and PRLR throughout the cycle. Telogen follicles showed only a very weak PRLR staining of ORS keratinocytes. The long-form PRLR transcript was shown by real-time polymerase chain reaction to be transiently down-regulated during early anagen, whereas PRL transcripts were up-regulated during mid anagen. Addition of PRL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle

Substantial Sex-Dependent Differences in the Response of Human Scalp Hair Follicles to Estrogen Stimulation In Vitro Advocate Gender-Tailored Management of Female Versus Male Pattern Balding

In this study, it was investigated how estrogens (17-β-estradiol, E2) affect the estrogen receptor (ER) expression and gene regulation of male versus female human scalp hair follicles in vitro. Anagen VI follicles from frontotemporal scalp skin were microdissected and organ-cultured for up to 9 d in the presence of E2 (1–100 nm). Immunohistochemistry was performed for ERβ-expression, known to be predominant in human scalp hair follicles, and for TGF-β2-expression (as negative key hair growth modulator), and E2-responsive genes in organ-cultured human scalp hair follicles (48 h, 10 nM) were explored by cDNA microarray, using a commercial skin focus chip (Memorec, Cologne, Germany). The distribution pattern of ERβ and TGF-β2-immunoreactivity differed between male and female hair follicles after 48 h culture. Of 1300 genes tested, several genes were regulated sex-dependent differently. The study reveals substantial sex-dependent differences in the response of frontotemporal human scalp hair follicles to E2. Recognition and systematic dissection of the E2-dependent gene regulation will be crucial for the development of more effective, gender-tailored management strategies for female versus male pattern balding