Exogen, the shedding phase of the hair cycle
-Kurt Stenn, M.D.
Director of Skin Biology Research Center
RW Johnson Pharmaceutical Research Institute
Hair serves the functions of camouflage, communication and protection from heat loss, trauma, infestation and sunlight. Inherent in hair growth is the ability to shed, thus cleansing the skin surface of adherent insects, bacteria, fungi and dirt and allowing for the adaptation of hair character and color to change environmental conditions. For this reason, hair shedding is crucial to normal health and social intercourse. Conversely, inappropriate shedding could be lethal to wild animals (example: animals without a proper fur coat in a cold environment would have mortal consequences) and psycho-socially destructive to humans. Adjusting to sudden massive hair loss, as in alopecia universalis, is profound, to say the least.
It has long been accepted that the hair cycle involves three phases: a growth phase (anagen), a regressing phase (catagen) and finally, a resting phase (telogen). Sometime at the end of the cycle the hair shaft sheds. At very specific times, the resting hair shaft base receives a signal, as yet unknown, which induces the shedding process. A good example of this process is fur growth in the mink or weasel in which there is rapid hair growth in the spring and fall but during the summer and winter the hair of the fur rests in telogen. Very little hair sheds during these long telogen periods. In early spring and late summer, the coat undergoes a molt preparing the pelt for the new hair growth and the changing season. It has long been recognized by animal breeders and pet owners that the molt is a well-defined and anticipated event. In fact, in this context, the molt has been recognized as a distinct part of the hair growth cycle. Recognizing this fact, and in keeping with the accepted terminology, the shedding phase was recently termed exogen (Stenn et al. 1998).
So, why is not the shedding function, the exogen phase, actually a subphase of telogen? Telogen is recognized as the phase of hair follicle growth when the follicle is completely quiescent. During this phase, the hair shaft sits firmly moored into the skin at the base of the follicle. This is the phase during which furriers harvest the pelt for commercial use. Shedding is, in fact, an active process which differs from the static telogen phase. Nevertheless, classically, shedding has been considered to be part of telogen. However, if one accepts that the process of shedding is different from the process of resting (as the process of follicle growth is different from the process of follicle regression), then in studying the hair growth cycle, one would logically separate the process of shedding from the other phases.
In order to analyze the exogen phase, Milner et al (2002) developed methodologies for measuring shedding hair. Using a mouse model, these workers found that shedding of non-cycling hair shafts peaks in the late anagen phase of the cycling hairs and that the shed hairs are the ones formed in a previous cycle. When a shed shaft root (base) is compared to a plucked telogen shaft root by light or electron microscopy, major morphological differences are apparent. The telogen root is made of packed nucleated cells which show intracytoplasmic fractures surrounding a cornified core making up the shaft. The exogen root, in contrast, is made of very few cells and these cells are separated at their outer edge by intercellular cleavage. The morphology of the hair root suggests that the exogen process involves a proteolytic event which occurs between the mooring cells of the telogen shaft base.
Previous studies do not elucidate the mechanism of exogen though they implicate desmoglein coherence (Koch et al 1998) and a proteolytic process. Desmoglein is a member of a family of cell to cell adhesion molecules and when its function is defective, telogen shafts are poorly moored in their follicles. In the literature, it is suggested that the outgrowing hair shaft "pushes" the resting shaft outward to effect shedding. That concept is unlikely since the resting hair shaft sits in its own epithelial-walled silo and, in many animal hair follicles, telogen shafts are retained in the follicle for several cycles. In humans, the fact that trichostatic conditions occur at all supports the notion that the transition from the resting follicle/shaft to the shedding shaft involves distinct processes.
Because the exogen, or shedding, phase is an important early element in all hair loss conditions, we need to understand more about its controls and seek pharmacological agents which impact its expression.
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In Chuong C-M (ed): Molecular Basis of Epithelial Appendage Morphogenesis. RG Landes Company, Austin, TX, pp 111-130, 1998.
Milner Y, Sudnik J, Filippi M, Kizoulis M, Kashgarian M, Stenn K. Exogen, shedding phase of the hair growth cycle:
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Koch PJ, Mahoney MG, Cotsarelis G, Rothenberger K, Lavker RM, Stanley JR. Desmoglein 3 anchors telogen hair in the follicle.
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