The fate of the hair follicle pigmentary unit during the cyclical involutio
n of anagen hair follicles is unknown. Using the C57BL/6 mouse model for ha
ir research, hair follicle melanocytes were examined during the anagen-cata
gen transformation, comparing spontaneous and pharmacologically induced cat
agen development. This study shows that both spontaneous catagen and dexame
thasone-induced catagen display similar changes in the pigmentary unit. Cat
agen hair follicles exhibited pigment incontinence in the dermal papilla an
d in selected outer root sheath keratinocytes, Melanocytes deleted by apopt
osis were detected in spontaneous catagen and, more commonly, in dexamethas
one-induced catagen, and were identified using transmission electron micros
copy by the presence of free premelanosomes in affected cells lacking epith
elial specializations, and by the colocalization of TUNEL positivity and ty
rosinase-related protein-1 immunoreactivity, By contrast, cyclophosphamide-
induced catagen was characterized by the initial retention of melanogenic a
nd dendritic melanocytes in the presence of widespread keratinocyte apoptos
is, Melanocyte incontinence and the ectopic distribution of melanin were mo
re severe than in the other forms of catagen, Whereas much of this melanin
was extruded, via the hair canal, to the skin surface, hair follicle-derive
d pigment was also detected within the epidermis, probably derived from pig
ment-carrying migrating outer root sheath keratinocytes from the proximal h
air follicle, Thus, apoptosis may account, at least in part, for the loss o
f melanogenic melanocytes during spontaneous catagen, Although dexamethason
e-induced catagen may provide a useful model for general hair pigmentation
research, catagen induced by cyclophosphamide offers an interesting model f
or studying the response, and relative resistance, of melanocytes to chemic
al injury.