After the completion of skin development, angiogenesis, i.e., the growth of
new capillaries from pre-existing blood vessels, is held to occur in the s
kin only under pathologic conditions. It has long been noted, however, that
hair follicle cycling is associated with prominent changes in skin perfusi
on, that the epithelial hair bulbs of anagen follicles display angiogenic p
roperties, and that the follicular dermal papilla can produce angiogenic fa
ctors. Despite these suggestive observations, no formal proof is as yet ava
ilable for the concept that angiogenesis is a physiologic event that occurs
all over the mature mammalian integument whenever hair follicles switch fr
om resting (telogen) to active growth (anagen). This study uses quantitativ
e histomorphometry and double-immunohistologic detection techniques for the
demarcation of proliferating endothelial cells, to show that synchronized
hair follicle cycling in adolescent C57BL/6 mice is associated with substan
tial angiogenesis, and that inhibiting angiogenesis in vivo by the intraper
itoneal application of a fumagillin derivative retards experimentally induc
ed anagen development in these mice. Thus, angiogenesis is a physiologic ev
ent in normal postnatal murine skin, apparently is dictated by the hair fol
licle, and appears to be required for normal anagen development. Anagen-ass
ociated angiogenesis offers an attractive model for identifying the physiol
ogic controls of cutaneous angiogenesis, and an interesting system for scre
ening the effects of potential antiangiogenic drugs in vivo.