634 REGENERATION AND GROWTH 7 



tabolic rate, thyroxin increases the activity of cytochrome c (Drabkin et al., 1950) 

 and of succinic oxidase (Barker, 1951). It inhibits lactic dehydrogenase, however, 

 and therefore presumably promotes fat-oxidation, through formation of acetyl- 

 coenzyme A, rather than the terminal oxidation of carbohydrate. Thyroidectomy, 

 indeed, causes fatty liver (Enteman et al., 1948). Thyroxin also accelerates the 

 oxidation of vitamin C (Gemmill, 1952) and so increases the requirement for this 

 vitamin and for the other antioxidant vitamins A and E (Drill, 1943), The action 

 on vitamin C is probably related to the interaction of both with phosphatases and 

 so with differentiation, in the connective tissues. Thyroid hormone would seem 

 to pass from a synergistic action with adrenal S-corticoids in the R-phase to some- 

 thing diametrically opposed in the late P-phase. 



As in normal growth (Marx et al., 1942; Scow, 1951; Gaunt, 1954) and in 

 amphibian metamorphosis, there is evidence of synergism between thyroid and 

 anterior pituitary (Richardson, 1945) but this may depend on the ACTH factor 

 rather than on the thyrotropic hormone or the pituitary growth-hormone, APGH, 

 which is thought to antagonise thyroid here (Willier, 1955). 



{Hi) Pituitary. Earlier results (Robertson, 1923) showing that extracts of the ante- 

 rior pituitary accelerate regeneration need re-investigation in view of the variety 

 of action of its various factors. The ACTH and thyrotropic principles promote 

 regeneration at appropriate time and concentration and this is probably true also 

 (Selye, 1955) of the growth-hormone (APGH). Thus Richardson (1945) and 

 Ten Gate and Uyldert (1944) recorded acceleration of regeneration in Amphibia 

 and Brues et al. (1936) in mammalian liver. Hypophysectomy prevents the regener- 

 ation of skull-bones and APGH restores this ability (Simpson, 1953). It stimu- 

 lates growth of the strengthening, connective tissues (Williamson and Neumann, 

 1954). Brues et al. (1936) observed a hyperplasia of all cells and an increase in 

 water, ash and protein in liver cells, — a rejuvenation process (J. Needham, 193 1). 

 On the other hand, Astarabadi et al. (1953) and Schotte's group (p. 631) detected 

 no positive action on liver- and limb-regeneration. Cuthbertson et al. (1941) 

 found (p. 628) that the hormone reduced nitrogen excretion, as in intact animals 

 (Li, 1950; Gavmt, 1954) bvit nevertheless did not speed up regeneration. William- 

 son and Neumann (1954), in fact, found an inverse relation between the two: low 

 concentrations of APGH (0.3 mg/rat, day) improved regeneration but decreased 

 nitrogen-retention, while i.o mg/day improved N-retention but gave poorer 

 healing than in controls. 



It seems possible that ACTH normally controls the R-phase and APGH the 

 P-phase of regeneration and that the latter therefore inhibits if administered too 

 early. The results of Schotte and Murphy (1953) and of Stone and Steinitz (1953) 

 do indicate a slight effect of the pitviitary in later stages. Even so, it is surprising 

 that the familiar growth-promoting action of APGH, and of the N-corticoids, is not 

 more evident during regeneration. 



{iv) Thymus. The endocrine status of this gland is questionable (Anderson, 1932) 

 notwithstanding the correlations between its changes in size (? activity) and the 

 processes of growth and maturation. Taken as a food it speeds regeneration (Kor- 

 schelt, 1927, p. 654) perhaps through its content of nucleic acid. There are his- 

 tological changes in the thymus of a guinea-pig while it is healing a fracture 



