CONTENTS 7 0 Riol. Rev. 37 20-2 J. Endocrinol. 17, 158-60. KOHN, R. (1958). Effect of administration of rat serum on rat liver regeneration. Exp. Cell Res. 14, 228-30. Kynarm A. H . English summary.) KUN, H. (1937). The effect of follicle hormone on the skin through local application: histologic studies in infantile and senile rats. Wien Klin. Wschr. 50, 408-1 I . LAHR, E. L. & RIDDLE, 0. (1938). Proliferation of crop sac epithelium in incubating and in prolactininjected pigeons studied with the colchicine method. Amer. J. Physiol. 123, 614-9.

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Summary Mitotic homeostasis: Mitotic control is maintained by the interaction of a tissue‐specific mitosis‐inhibiting chalone, which permeates the whole tissue, and a non‐tissue‐specific mitosis‐promoting mesenchymal factor, which originates in the connective tissue and acts only on connective‐tissue‐adjacent cells. In the basal layer of the epidermis the mitotic rate is determined by the relative concentrations of these two substances; in the distal layers the chalone is dominant so that all cells must become post‐mitotic, age, and die. Thus the perfect balance between cell gain and cell loss that is maintained equally in hypoplasia, normality, and hyperplasia is ensured by the fact that all cells forced distally by mitotic pressure enter a chalone concentration that is high enough to direct them into post‐mitosis and so to their deaths. The mitotic rate of the basal epidermal cells and the ageing rate of the distal cells are both inversely related to the chalone concentration. A change in the mitotic rate is matched by an equal change in the ageing rate so that, within limits, epidermal thickness (or mass) remains constant. Epidermal thickness is determined by the tissue‐specific ratio, mitotic rate: ageing rate; it is influenced by the mitotic rate only when this exceeds a certain critical level. Evidently all epithelial tissues, even when these form solid masses (e.g. liver hepato‐cytes), have a similar control mechanism, the ‘basal cells’ being those that are connective‐tissue‐adjacent and the ‘distal cells' those that are not. Tissues that are not connective‐tissue‐based (e.g. erythrocytes and granulocytes) have specialized mechanisms involving differentiation from relatively undifferentiated stem cell populations, as also do the connective tissues themselves. Local tissue damage leads via local chalone loss to a temporarily and locally increased mitotic rate; chronic damage leads via chronic chalone loss to hyperplasia, the increase in tissue mass being limited by the reduced life‐span of the post‐mitotic cells. Compensatory hypertrophy When a tissue mass is so large (e.g. the hepatocytes) in relation to the total body mass that the escaping chalone forms a significant systemic concentration, extensive damage leads to compensatory hypertrophy. The reduced tissue mass (e.g. after partial hepatectomy) produces less chalone, leading to a reduced systemic concentration, and therefore a higher chalone loss from the surviving tissue. This results in a general mitotic response in that tissue, as the relative power of the mesenchymal factor increases, and thus to an increase in tissue mass. Growth ceases when the normal tissue mass is attained. When a large tissue suffers chronic damage (e.g. liver cirrhosis) the chronic chalone lack results in hypertrophy, which is limited by the reduced life‐span of the post‐mitotic cells. Tumour growth Mitotic control is lost when the chalone concentration falls so low that the ‘distal cells’ remain mitotic; cell gain then exceeds cell loss and a tumour appears. Such chalone...