VII INTERNAL FACTORS 633 



seems plausible, since a serious disability in either sex would be biologically 

 intolerable. However Needham (1949) found regeneration faster in the male 

 Asellus than in a female of the same body-size. Emery (1937) failed to stimulate the 

 regeneration (compensatory hypertrophy) even of the ovary itself, using oestro- 

 gens. 



(n) Thyroid. There is now a wealth of evidence that thyroid hormone is essential 

 for healthy regeneration in vertebrates (Table 14). It is paradoxical that whereas 

 the adrenal cortex, producing two types of factor, promotes only the R-phase of 

 regeneration, the thyroid, with only one factor, assists both phases, just as it pro- 

 motes all phases of ontogenesis (Brody, 1945, p. 168). It has been shown to im- 

 prove various R-phase activities, — phagocytosis (Menkin, 1940, p. 94), the pro- 

 liferation of leucocytes (Ponder and Flint, 1927), and nitrogen-flow (De Gribble 

 and Peters, 1951). Methionine, which reduces nitrogen flow also prevents the loss 

 of weight of hyperthyroid animals (Gaunt, 1954). Thyroxin stimulates the activity 

 of the adrenal cortex (Gaunt, 1954) and may affect nitrogen-flow in this way. 

 Thyroxin and the gkicocorticoids both accelerate metamorphosis in the toad 

 (Frieden and Naile, 1955) a process with many similarities to regeneration 

 (J. Needham, 1942). The androgenic corticoids, and androgens themselves, retard 

 metamorphosis while the effect of oestrogens resembles that of "S" corticoids. 



Peadon (1953) found that anti-thyroid agents inhibited mitosis but the general 

 view is that thyroid itself retards rather than promotes cell-division (Peter, 1945; 

 Mittler and Herman, 1950; Smelzer and Ozanics, 1954). 



The hormone tends to accelerate regeneration but to reduce the final size 

 (Korschelt, 1927) just as it does in normal growth (Brody, 1945). It therefore 

 promotes differentiation (Peadon, 1953; Hess and Kopf, 1951; Jaques, 1950) 

 rather than growth. Steinlin (1900) found the hormone most essential for the later 

 stages of regeneration. The phase-specificity therefore is essentially the same as 

 that of the phosphatases and it may be significant that thyroxine increases the 

 activities of acid and alkaline phosphatases and of adenosinetriphosphatase (Bar- 

 ker, 1 951) and that it depletes the liver of alkaline phosphatase (Kochakain and 

 Bartlett, 1948). Again it stimulates the turnover of the terminal phosphate of 

 ATP (Venkataraman et al., 1950). It seems clear that thyroxin normally controls 

 the coupling between oxidative reactions and the useful manipulation of energy 

 through phosphorylation-processes. Antithyroid substances, such as the nitroana- 

 logue, dinitrophenol (DNP) uncouple phosphorylation from oxidation (Glass, 

 1952). Thyroxin itself in high concentration (Glass, 1952; Klemperer, 1955) acts 

 as an uncoupler while low concentrations of DNP promote regeneration (Cuthbert- 

 son, 1944). This may explain the many claims that excess thyroid hormone retards 

 regeneration (Pawlowsky, 1923; Torrey, 1934; Richardson, 1945; Drabkin et al., 

 1950; Kambara, 1953; Smelzer and Ozanics, 1954). The indigenous thyroid is 

 normally working at optimal concentration, or possibly sometimes rather above 

 this level (Comsa, 1952; Stone and Steinitz, 1954). Excess thyroid causes much 

 the same symptoms as a deficiency (Gaunt, 1954). Both cause increased nitrogen- 

 loss (Carter and Thompson, 1953, p. 214) so that the physiological action is to 

 retain rather than to squander nitrogen. 



As part of its action on oxidative procc-ses and the familiar stimulation of me- 



I.iterature p. 641) 



