P6.57 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

F Conrad¹, U Ohnemus¹, B Gerstmayer², A Bosio², A Bettermann¹, E Bodo¹ , R Paus¹

¹Dept. of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, D-20246 Hamburg, Germany ²Fa memorec, Cologne, Germany

Estrogens (17-ß-estradiol, E2) profoundly modulate hair growth, acting largely as hair growth inhibitors. Here, we investigated how E2 affects the growth, 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 days in the presence of E2 (1-100nM). Immunohistochemistry was performed for ERß-expression, known to be predominant in human scalp hair follicles, and E2-responsive genes in  organ-cultured human scalp hair follicles (48 hrs, 10nM) were explored by cDNA microarray, using a commercial skin focus chip (memorec, Cologne).

Hair shaft elongation of female hair follicles was significantly inhibited by  1-100nM E2, starting on day 5 to day 9 of the culture period (1nM, p<0.001). In striking contrast, hair shaft elongation in male hair follicles was significantly stimulated by 1-100nM E2 during the whole culture period (10nM, p<0.001). This correlated with a significant increase of proliferating (Ki67+) hair matrix keratinocytes on day 9 (10nM, p<0.05). As in female frontotemporal follicles, the duration of anagen was slightly prolonged in E2-treated male hair follicles compared to controls. The distribution pattern of ERß-immunoreactivity also substantially differed between male and female hair follicles after 48hrs culture (female: predominant in the dermal papilla, male: predominant in matrix cells). Of 1300 genes tested, more than 600 E2-responsive genes (<0.5fold suppressed or > 1.5fold stimulated) were detected in human hair follicles. Several genes were modulated in both sexes (e.g. down-regulation of SPP1; up-regulation of K6HF). In addition, sex-dependent differences in E2-mediated gene regulation were detected (e.g., for BMP7, EPS8 [belongs to the epidermal growth factor receptor-pathway], CYR61[homolog of insulin-like growth facto-binding protein], FOS-like antigen2).

In conclusion, this study reveals substantial sex-dependent differences in the response of frontotemporal human scalp hair follicles to E2, which are likely based on significant E2-dependent gene regulation differences. Recognition and systematic dissection of these differential E2 responses will be crucial for the development of more effective, gender-tailored management strategies for female versus male pattern balding.