10 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS the adipose or subcurls layer which are associated with phases of the hair growth cycle. The skin is thus a highly integrated and cyclic system and yet there is considerable autonomy, since different areas on the body can be in different physiologic states at any given time. There is a vertical integration but a limit to lateral influences. It is easy to see the value to the organism of such a situation, keeping disturbances localized, so to speak, but what is the mechanism ? Also there is no conclusive answer as yet to the question of what initiates a hair follicle to produce a hair and what, after a certain time, causes the follicle to cease producing a hair. The observations to be reported in this paper on the physiology and histochemistry of hair growth do not answer these basic questions but rather emphasize the im- portance of these two unanswered questions for our eventual understanding of the physiology and pathology of the skin. The basic similarity of all mammalian skin is evident. There are dif- ferences, however, and one of these may be pertinent to the present dis- cussion. For instance, man and the guinea pig differ from the mouse, rat, hamster, and rabbit in not having waves of hair growth. The hairs of man and the guinea pig are not synchronized in their growth, each hair going through its cycle without relation to its immediate neighbors. Tenta- tively it would appear that if follicles are less than one-half or one-third of a millimeter apart, as they are in many mammals, they can "communicate" and thus result in a wave. In any highly integrated system it is meaningless to designate any one component as the "master" component, since they are all necessary for normal function. The term "central component" may be used, perhaps, with more validity. Such a component is the upper external sheath of the hair follicle, the "permanent" portion (2). This upper external sheath is continuous with the basal layer of the adjoining epidermis and is also con- tinuous with the peripheral cells of the sebaceous gland. In the resting phase, telogen, of the hair growth cycle, this upper sheath is the whole follicle. Its lower end, the "germ," is in contact with the resting dermal papilla, which is continuous with the contracted connective tissue sheath around the follicle. The brush-like club end of the hair is anchored in this follicle just above the lower "germ" end and just below the opening of the duct of the sebaceous gland. When this follicle again becomes active, i.e., enters anagen, there is in- creased mitotic activity not only in this sheath but also in the adioining basal layer of the epidermis and peripheral cells of the sebaceous gland (5). Rapidly a lower external sheath is added and the bulb surrounding the dermal papilla is at the end of it. The dermis and especially the adipose layer thicken at this time. Histochemically, the most striking aspects of this early anagen are the tremendous, accumulation of glycogen in the cells of the newly added lower external sheath and the appearance of mucopoly-

PHYSIOLOGY AND HISTOCHEMISTRY OF HAIR GROWTH 11 saccharides (metachromasia) in the dermal papilla (11). Whereas esterase is abundant in the resting follicle, the active follicle has, especially in the lower external sheath and the bulb, an abundance ofsuccinic dehydrogenase (Argyris, unpublished), indicating increased oxidative metabolism. These changes are presumably involved in the large energy supply soon to be re- quired for rapid hair production. Immediately following these changes, the phase of active hair production starts. The bulb, especially its lower por- tion, has a much increased mitotic activity, but the remainder of the follicle, the basal epidermis, and the peripheral sebaceous cells have less, as if being drained by the mitotic activity of the bulb. Glycogen is observed in cells of the upper bulb but disappears as keratinization progresses. Changes in the distribution of sulfhydryl groups can also be observed, extending from the bulb out to the region where keratinization is complete (7). The --SH groups are particularly abundant in regions which are parakeratotic. The cessation of hair production is very rapid. Mitotic activity ceases in the bulb, glycogen disappears from the lower external sheath, metachro- masia disappears from the dermal papilla, the last keratinizing cells form the club instead of becoming inner sheath or hair, and by a massive degenera- tion of most of the cells of the lower external sheath and bulb, the resting stage again occurs with the upper external sheath intact. If the connective tissue sheath fails to shorten radically at this time, as in the hairless geno- type of the mouse (2), a normal anchoring club does not form and the lower follicle breaks up into small isolated portions. The dermal papilla is thus stranded in the adipose layer and is not in the proper position to induce a new hair growth from the intact upper sheath. The isolated fragments produce sebaceous and later keratinized cysts. Without normal hair cycles, the epidermis gradually becomes thicker and wrinkled and latent pigment cells become melanogenically active. Damage to the epidermis from methylcholanthrene is less severe when the treatment occurs at the time of hair growth in the treated area (4, 8). The sebaceous glands are lost completely in four days regardless of phase of the hair cycle but are restored from the cells of the upper external sheath by lipid accumulation in these cells. This restoration is much more rapid when the hair cycle is in an anagen phase at the time (10). When a wound is made in the skin of a mouse, surgically or x-irradiation induced, the ex- ternal sheaths at the edge of the wound are involved in the formation of the epithelial tongues over the wound (1). Normally the epidermis produces a constantly sloughing corneum and the sebaceous gland continuously produces sebum, but the sheath pro- duces a hair-producing apparatus only in cycles. Plucking of resting or club hairs will initiate a new growth in the area plucked. In man and the guinea pig, plucking of resting hairs will also cause new growth, but it ap- pears less dramatic because many of the hairs in a given area are growing