title: Inhibitory effects of progestogens on the estrogen stimulation of melanocytes in vitro.
abstract: BACKGROUND
  The use of oral estrogen-progestogen contraceptives may cause melasma, an epidermal hyperpigmentation in sun-exposed areas of the face. It is assumed that elevated estrogen levels lead to the activation of melanocytes, while the role of the gestagen component of contraceptives in pigmentation remains unclear and may vary between the different progestogens. In this study, we analyzed the distinct effects of progesterone and chlormadinone acetate (CMA) on melanocytes in comparison with estrogen.
  
  
  METHODS
  Human melanocytes were exposed to different concentrations of 17beta-estradiol and progestogens and analyzed for proliferation by a fluorometric cell viability assay and for pigmentation by a (3)H-labeled tyrosine assay. Subgroups of cells were additionally irradiated with UVA or UVB.
  
  
  RESULTS
  Proliferation of melanocytes was induced by 17beta-estradiol (0.1 and 1 nM) in approximately half of the experiments, while progesterone (100 nM) and CMA (100 nM) reduced the proliferation rate by 38% and 27%, respectively. The pigmentation activity was slightly stimulated by 17beta-estradiol, whereas progestogens had no effect on the tyrosinase activity.
  
  
  CONCLUSIONS
  Our data suggest that progesterone and CMA can inhibit proliferation of human melanocytes, which counteracts the stimulatory effects of estrogen. This may be of relevance for the choice of progestogen in oral contraceptives to prevent the development of melasma.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wiedemann
authors.forename: Ursula
authors.initials: U
authors.lastname: Nägele
authors.forename: Georg
authors.initials: G
authors.lastname: Schramm
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002715:Chlormadinone Acetate / Q000494:pharmacology*; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008548:Melanosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D011374:Progesterone / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D003280:Contraceptives, Oral, Synthetic; D002715:Chlormadinone Acetate; D011374:Progesterone; D004958:Estradiol; D014442:Monophenol Monooxygenase