Emj. Peters et al., Hair-cycle-associated remodeling of the peptidergic innervation of murine skin, and hair growth modulation by neuropeptides, J INVES DER, 116(2), 2001, pp. 236-245
As the neuropeptide substance P can manipulate murine hair growth in vivo,
we here further studied the role of sensory neuropeptides in hair follicle
biology by determining the distribution and hair-cycle-dependent remodeling
of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-rel
ated peptide, substance P, and peptide histidine methionine (employed as va
soactive intestinal peptide marker) were identified by immunohistochemistry
, All of these markers immunolocalized to bundles of nerve fibers and to si
ngle nerve fibers, with distinct distribution patterns and major hair-cycle
-associated changes. In the epidermis and around the distal hair follicle a
nd the arrector pill muscle, only calcitonin-gene-related peptide immunorea
ctive nerve fibers were visualized, whereas substance P and peptide histidi
ne methionine immunoreactive nerve fibers were largely restricted to the de
rmis and subcutis. Compared to telogen skin, the number of calcitonin-gene-
related peptide, substance P, and peptide histidine methionine immunoreacti
ve single nerve fibers increased significantly (p<0.01) during anagen, incl
uding around the bulge region (the seat of epithelial stem cells). Substanc
e P significantly accelerated anagen progression in murine skin organ cultu
re, whereas calcitonin-gene-related peptide and a substance-P-inhibitory pe
ptide inhibited anagen (p<0.05). The inhibitory effect of calcitonin-gene-r
elated peptide could be antagonized by coadministrating substance P. In con
trast to substance P, calcitonin-gene-related peptide failed to induce anag
en when released from subcutaneous implants. This might reflect a different
ial functional assignment of the neuropeptides calcitonin-gene-related pept
ide and substance P in hair growth control, and invites the use of neuropep
tide receptor agonists and antagonists as novel pharmacologic tools for the
rapeutic hair growth manipulation.