title: Melanocyte and gonad activity as potential severity modifying factors in C3H/HeJ mouse alopecia areata.
abstract: Circumstantial evidence has previously suggested gonad derived steroid hormones and melanogenesis related antigens may modify human alopecia areata (AA). AA-like hair loss can be induced in C3H/HeJ mice after skin allografts from spontaneous AA-affected mice. This inducible model was used to evaluate hormones and hair follicle melanocyte presence as disease-severity modifiers. Ten females and 9 males were gonadectomized and received AA-affected allografts. All gonadectomized mice had 2-4 weeks delay in AA onset relative to non-gonadectomized controls. Two females and 4 males failed to develop any AA by 25 weeks after grafting. The experiment was repeated with gonadectomized female and male mice plus non-gonadectomized mice subcutaneously implanted with silastic capsules containing 80 microg 17beta estradiol or 10 mg 5alpha dihydrotestosterone, respectively. Five of 11 ovariectomized and 9 of 11 non-ovariectomized, estradiol supplemented females developed AA with extremely rapid progression. Three of 8 castrated, but none of 11 non-castrated, dihydrotestosterone-supplemented males expressed AA. In a separate study, 14 mice were freeze-branded, producing white hair on the dorsal lumbar region, and later received full-thickness allografts. Thirteen mice developed patchy pigmented and non-pigmented hair loss. One mouse developed diffuse, pigmented hair loss, but with white hair survival persisting 25 weeks after grafting. The results suggest that gonadal steroid hormones can modulate C3H/HeJ mouse AA where estradiol promoted rapid progression of AA while dihydrotestosterone increased resistance to AA onset. In general, both pigmented and non-pigmented C3H/HeJ mouse hair is susceptible to AA. Murine AA susceptibility and severity clearly involves an interplay between genetic and epigenetic factors.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA. kevin@keratin.com
authors.forename: K J
authors.initials: KJ
authors.lastname: McElwee
authors.forename: K
authors.initials: K
authors.lastname: Silva
authors.forename: W G
authors.initials: WG
authors.lastname: Beamer
authors.forename: L E
authors.initials: LE
authors.lastname: King
authors.forename: J P
authors.initials: JP
authors.lastname: Sundberg
mesh_terms: D000506:Alopecia Areata / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006066:Gonads / Q000502:physiology*; D008297:Male; D008544:Melanocytes / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D009919:Orchiectomy; D010052:Ovariectomy; D012720:Severity of Illness Index
chemical_list: D013196:Dihydrotestosterone; D004958:Estradiol