llxp ncrnuiliil IW4: .i'," • /.' ) .^(1 I'riiih'd ill nainnirk • All iii;lil\ IV94 Experimental Dermatology ISSN ()'M)6-6705 Murine skin as a target for melatonin bioregulation Slomiriski A, Chassalevris N; Mazurkiewicz J; Maurer M; Paus R. Murine skin as a target for tnelatoniti bioregulation, Fxp Dertnatol 1994: 3: 45-50, in M^ttnksgaard, 1994 Abstract: Specific bitiding sites for 'H-tnelatonin were detected iti mem- brane fractions prepared frotn C57 BL-6 tnouse skin, and were localized to the epidermis and the epithelial bulb of the hair follicle by //; situ autoradiography. In skin organ culttrre, melatoniti stimulated DNA synthesis by the epidermal keratinocytes at concentration 0.1-10 tiM, while at > 1 ).tM it itiiiibited tyrosinase activity. We eoriehtded that murine skin is a tamel for melatoniti bior'eeulation. Aiidrzej Nikolaos Chassalcvris^ Joseph IVlazurkiewicz\ Marcus Maurer"* and Ralf 'Department ol Pathology and Laboratory Medi- cine, ^Department ol Microbiology, Immunology and Molecular Genetics, ^Department of Anat- omy, Cell Biology and Neurobiclogy, Albany Medi- cal College, Albany, NY, USA, and ''Department of Dermatology University Hospital R. Virchcw, Freie Universitaef Berlin, Berlin, Germany Key words: melatonin - skin - keratinocytes - C57 BL-6 mouse Dr. Andrzej T. Slominski, Department of Pathol- ogy and Laboratory Medicine, 47 New Scotland Avenue, Albany Medical College, Albany NY 12208, USA. Tel. (518) 262-5454: FAX (518) 2625748. Accepted for publication 22 December 1993 Introduction The skin and ils appctidages arc recognized target organs for tnultiple hormones atid neuropetides (1-4), While this is appreciated for steroid and thyroid hortnones, insulin growth factor-1 (IGF- 1), proopiomelanocottin products and cathechola- tnines (1-5), it has remained uticlcar whether the pineal neurohormone melatonin plays any role in skin physiology (6-8), In mammals, the indolamine tnelatonin is considered to serve as the tnain signal tnolecule for linking an external Zeitgeber, the photoperiod, to metabolic, endocrine and immuno- logical changes, whose wide range is only gradually being elucidated (6, 8), Melatonin is a product of the multistep conversion of L-tryptophan to serotonin, then N-acetyl-serotonin and subse- quently tnelatonin, and is synthesized in the pineal gland, retina and Flarderian gland (8), It is ac- cepted that multiple regulatory functions of mela- tonin are tnediated by the interaction with specific cell surface receptors (9), Such receptors have been characterized iti the cetitral nervous system, endo- crine organs and the spleen (8, 9), While its general role in tnamtnalian pigment cell biology is still uncertain and controversial (6, 7, 10), tnelatonin was seen to inhibit melanin syn- thesis in hamster hair follicles (II) and to inhibit tnelanogenesis and cell ptoliferation in cultured rodent melanotna cells (12), In mammalian skin, high doses of melatonin were reported to initiate pretnature winter fur growth in mink (13) and to t educe the development of an epidertnal derivative, the tnamtnary gland, in nortnal mice (14), In ad- dition, seasonal variations of physiological hair growth and loss, including male pattern hair loss, are well-recognized (1,4, 15), Melatonin has been implicated in the pathogenesis of vitiligo (7, 16) and abnormal melatonin serutn levels were noted in patients with psoriasis (17), atopic eczema (18), and tnelanoma (19), In addition, the incidence atid course of several skin diseases is appreciated to display seasonal dependence (15), Therefore, we have examined in this pilot study whether specific tnelatonin binding sites are present in skin, and whether melatonin can alter ketatinocyte prolifer- ation and melanogenesis in intact, histocultured skin //; vitro. As an experimental model, we have used the well-characterized C57 BL-6 tnouse model for hair growth and pigmentation studies (20-24), 45