The Control of Epidermal Thickness*

Abstract

Summary.— Epidermal mass (thickness) is controlled by a complex mechanism in which the epidermal chalone plays a central role. The chalone inhibits epidermal mitotic activity by reducing the proportion of the basal cells that are in the mitotic cycle and the speed at which this cycle is completed. It also acts to reduce the speed at which the distal post‐mitotic cells age and die. The response of the epidermal mass (thickness) to a rising mitotic rate (falling chalone concentration) is divisible into 3 separate phases. In Phase 1 (e.g. normal mouse epidermis) the mitotic rate is low. Mitosis occurs in the basal layer in such a way that the 2 daughter cells remain basal; the pressure so generated is relieved by the extrusion of a neighbouring basal post‐mitotic cell. Any change in the mitotic rate is matched by an equivalent change in the rate of ageing of the extruded cells; thus no change in epidermal thickness occurs. In Phase 2 (e.g. normal human epidermis, hyperplastic mouse epidermis) the mitotic rate has increased beyond the point at which all the basal cells have entered the mitotic cycle; there are therefore no post‐mitotic basal cells available to be extruded. From this point onwards the greater the mitotic rate (the lower the chalone content), the higher the lateral pressure within the basal layer, the greater the folding (or doubling) of this layer, the higher the numbers of basal mitotic cells per unit area of skin, the higher in consequence the number of distal post‐mitotic cells (which are also ageing more quickly) per unit area of skin, and the thicker the epidermis. Thus epidermal mass (thickness) is a function of the degree of folding (or doubling) of the basal layer and of the increased rate of post‐mitotic ageing. Towards the top of Phase 2 (e.g. psoriasis, papillomata) the chalone content of the whole epidermis has fallen to a low level, but the rate of cell gain still equals the rate of cell loss. In Phase 3 (e.g. epidermal carcinomata) the average chalone content is very low, and the rate of cell gain exceeds the rate of cell loss. The normal balance can be restored by raising the chalone concentration artificially. The manner in which this mechanism operates during normal healing and tissue regeneration is examined, and reasons are given for considering that these epidermal reactions are typical of mitotic tissues and of tumours in general.

Human Epidermal Cell Proliferation with Regard to Circadian Variation of Plasma Cortisol

“…for maintaining constant thickness of the epidermis [Weiss and Kavanau, 1957;Iversen, 1961Iversen, , 1969Mercer, 1962;Bullough, 1972]. Chalones, stress hormones (glucocorticoids, catecholamines) and the cyclic AMP/GMP system play an important part in the control of epidermal cell proliferation [Houck and Daugherty, 1974;Voorhees et al, 1976;Wilson and Marks, 1976].…”

Epidermal repair in chronic venous ulcers

“…The greater activity in the region of the first 100 basal cells indicates that a true increase in mitosis is present at the ulcer edge, a situation which would be compatible with a persisting low local concentration of mitotic inhibitor or chalone due to the unepithelialized area (Bullough, 1973). The increase in epidermal thickness at the ulcer edge is further evidence for an increase in mitosis since in human epidermis increase in mitosis is associated with increase in epidermal thickness (Bullough, 1972). If epidermal cells are still being produced at the margins of non-healing lesions, the lack of production of new cells would not appear to be the reason for the failure of epithelialization, and there must be some other fundamental cause such as failure of cells to adhere to one another or their substrate.…”

Effect of heat and cold stressors on skin thickness and wound outline retention 24 h after excision

“…Collagen and hence skin thickness and firmness are reduced by the inhibitive action of glucocor ticoids on fibroblast, fibrin, and exudate for mation [A!rich et ah, 1951;Spain and Molomut, 1952;Perasalo et ah, 1953; also, long bone cortical thickness is reduced in heat-and cold-exposed rats and mice; Riesenfeld, 1976;Brandt and Siegel, 1978]. Bullough [1972] has also shown that reduction of skin thickness may be due to the interaction of glucocorticoids and epi dermal chalone, resulting in decreased mito tic efficiency.…”