Keratinocyte apoptosis is a central element in the regulation of hair
follicle regression (catagen), yet the exact location and the control
of follicular keratinocyte apoptosis remain obscure. To generate an ''
apoptomap'' of the hair follicle, we have studied selected apoptosis-a
ssociated parameters in the C57BL/6 mouse model for hair research duri
ng normal and pharmacologically manipulated, pathological catagen deve
lopment, As assessed by terminal deoxynucleotide transferase dUTP fluo
rescein nick end-labeling (TUNEL) stain, apoptotic cells not only appe
ared in the regressing proximal follicle epithelium but, surprisingly,
were also seen in the central inner root sheath, in the bulge/isthmus
region, and in the secondary germ, but never in the dermal papilla. T
hese apoptosis hot spots during catagen development correlated largely
with a down-regulation of the Bcl-2/Bax ratio but only poorly with th
e expression patterns of interleukin-1 beta converting enzyme, p55(TNF
R), and Fas/Apo-1 immunoreactivity. Instead, a higher correlation was
found with p75(NTR) expression. During cyclophosphamide-induced follic
le dystrophy and alopecia, massive keratinocyte apoptosis occurred in
the entire proximal hair bulb, except in the dermal papilla, despite a
strong up-regulation of Bar and p75(NTR) immunoreactivity. Selected r
eceptors of the tumor necrosis factor/nerve growth factor family and m
embers of the Bcl-2 family may also play a key role in the control of
follicular keratinocyte apoptosis in situ.