Melanocyte and gonad activity as potential severity modifying factors in C3H/HeJ mouse alopecia areata

Circumstantial evidence has previously suggested gonad derived steroid horm ones and melanogenesis related antigens may modify human alopecia areata (A A). 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 evaluat e hormones and hair follicle melanocyte presence as disease-severity modifi ers. Ten females and 9 mates were gonadectomized and received AA-affected a llografts. 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 gonadec tomized female and male mice plus non-gonadectomized mice subcutaneously im planted with silastic capsules containing 80 mug 17 beta estradiol or 10 mg 5 alpha 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-cast rated, dihydrotestosterone-supplemented males expressed AA. In a separate s tudy, 14 mice were freeze-branded, producing white hair on the dorsal lumba r region, and later received full-thickness allografts. Thirteen mice devel oped patchy pigmented and non-pigmented hair loss. One mouse developed diff use, pigmented hair loss, but with white hair survival persisting 25 weeks after grafting. The results suggest that gonadal steroid hormones can modul ate C3H/HeJ mouse AA where estradiol promoted rapid progression of AA while dihydrotestosterone increased resistance to AA onset. In general, both pig mented 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.