F Conrad, H Kobayashi, A Bettermann, B Tychsen, R Paus

Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany

Cross connections may exist between estrogen receptor signalling and melatonin (N-acetyl-5-methoxytryptamine), since melatonin reportedly suppresses estrogen receptor (ER) expression and transactivation in selected breast carcinoma cells in vitro. Given that breast epithelium is an epidermal derivative and shows some similarities to hair follicle epithelium, we have investigated whether melatonin (1pM-10nM) modulates ER expression in vitro in organ-cultured murine skin and human scalp hair follicles.

Three groups of C57BL/6-mice skin in different hair cycle stages (telogen, anagenVI, catagen, n=5) were examined after a 6-12hrs skin-organ-culture. Microdissected human female frontotemporal scalp hair follicles were organ-cultured for 48hrs.

Compared to the vehicle controls, the RNA-levels of ER-ß, as measured by semi-quantitative RT-PCR, decreased in the back skin of the animals with all hair follicles in the catagen and telogen stage of the hair cycle after 6h of culture and treatment with 10pM melatonin (suggesting an effect mediated by melatonin membrane receptors). ER- RNA-levels became almost undetectable in all groups and could therefore not be further assessed. This was confirmed on the protein level: after 6 hrs of melatonin stimulation in organ culture, melatonin-treated murine skin samples showed a decreased ER-ß immunoreactivity, especially in the dermal papilla of telogen and catagen hair follicles. In human female scalp hair follicles, immunoreactivity for ERß decreased after application of low-dose melatonin (1-100pM), as measured by quantitative immunohistomorphometry.

The limited currently available data suggest the existence of intriguing, novel  (direct or indirect) interactions between melatonin and estrogen signalling in normal murine skin and normal human scalp hair follicles, whose molecular basis, endocrinological functions and clinical implications remain to be elucidated.