136 KERATIN AND KERATINIZATION 



mouse, and these probably occur elsewhere. The maximum epidermal 

 mitotic activity occurs during sleep and the minimum during muscular 

 exercise. Among humans the maximum of mitosis occurs at night, again 

 the period of rest. 



Epidermal cells need a supply of energy for mitosis and division, for the 

 synthesis of their specialized products and for keratinization when this 

 occurs. Carbohydrates are the main source of energy and these are 

 probably supplied as glucose and stored as glycogen. Glycogen is not 

 found in the germinal layers, but may occur in the prickle cell layers 

 (Bradfield, 1951) and is stored in quantity in the outer root sheath of the 

 hair. The energy of the glucose probably becomes available in anoerobic 

 glycolysis through the agency of the tricarboxylic Krebs acid cyclic 

 (Bullough and Johnson, 1951 ; Bullough, 1952). Many of the intermediate 

 substrates of the Krebs cycle can be utilized by skin and have been found 

 in hair roots (Bullough, 1958). Rothman (1954) believes there may be other 

 pathways specific to skin. Bullough (1952) found that many of the inter- 

 mediate substrates of the Krebs cycle will support cell division, and was 

 thus led to suppose that mitosis required energy and could only occur 

 when the cells are able to absorb adequate amounts of carbohydrates and 

 oxygen. That is, the special necessities for mitosis are stored in some form 

 during antephase and are syphoned off when division commences. Were 

 this the case muscular activity may well lead to short supplies in the 

 epidermis and delay preparations for division. The diurnal cyclic activity 

 of the epidermal cells is thus seen as an indirect consequence of the cylic 

 muscular activity induced by diurnal fluctuations of light. The cycle is 

 absent in skin cultivated in vitro, thus clearly demonstrating its dependence 

 on extracellular factors. More recently Bullough and Laurence appear to 

 have abandoned this opinion (Bullough and Laurence, 1958). Further, 

 having found that, in the skin of starved rats in which the number of 

 mitoses is very much reduced there is a dramatic burst to several times the 

 normal number when skin is removed and transferred to saline (in absence 

 of oxygen and glucose), Bullough and Laurence (1961) conclude that 

 epidermal cells are always able to complete preparations for division, but 

 that some factor inhibits the process in early prophase. They give reasons 

 for believing that it is the high adrenalin levels associated with muscular 

 activity which inhibit these cells. Thus the epidermal rhythm is linked 

 with the rhythmic changes in adrenal activity (see p. 144). 



Bullough's general conclusion, that glucose and its subsequent con- 

 version to yield energy is a critical factor controlling mitosis, has not been 

 accepted without question. In a series of papers Gelfant (1958, 1959a, 

 1959b) has confirmed the participation of glucose, but insists that an 

 adequate supply of glucose and oxygen alone will not stimulate mitosis in 

 intact mouse ear epidermis; the mitogenic factor may be the cutting. This 



