VII INTERNAL FACTORS 639 



of promoting the synthesis of homologous protein autocatalytically. He further 

 postulates that the inhibitor is related to it as antibody to antigen. In fact a promo- 

 tor inhibitor (PI) complex has been detected by Marshak and Walker (1945) in 

 mammalian liver, and by Teir (1952) in the orbital gland of the rat. In the orbital 

 gland-extract the promotor is at first inactive or masked, possibly by the inhibitor. 

 This masking no doubt would increase with the production of inhibitor in the later 

 stages of regeneration. Wounding, like extraction techniques, probably frees the 

 promotor from the inhibitor. Beryllium may inhibit the breakdown of the complex 

 (p. 626). 



If, as seems probable, there is a PI pair for every organ and tissue, then a very 

 large number may be involved in any extensive regeneration, and a non-specific 

 increase in serological reactions generally (p. 638) is to be expected. At present 

 there is no evidence that when an organ is amputated, the non-specific tissues, — • 

 connective tissues, muscle, etc. — are stimulated in non-homologous organs so that 

 it may even l^e necesary to envisage a PI pair for every tissue of every organ, a 

 detailed specificity which compares with that postulated by Sperry (1951) be- 

 tween each nerve and its end-organ. 



Some of the inhibitor of the Tiibularia hydranth diffuses out into the water 

 (Rose and Rose, 1941 ; Tardent, 1955) and such washing-out may relieve regenera- 

 tion in aquatic animals more generally. Ludwig and Ludwig (1954) have postu- 

 lated such a process to explain compensatory reversal of opercular type in the 

 serpulid, Hydrioides, — that is the growth of the vestigial operculum of one side of 

 the body to replace the amputated, functional operculum of the other side. 



Balazs and Holmgren (1949) found increasing amounts of a growth-inhibitor 

 in the albumin-fraction of the serum in later stages of regeneration. Later ( 1 950) 

 they attributed its origin to basophilic material, probably mucopolysaccharides 

 or mucoprotein of the differentiating dermis. Mucoprotein could be resolved into 

 heat-labile protein and heat-stable, non-protein, prosthetic components, and it 

 is conceivable that such a change in this type of factor may explain the discrepan- 

 cy between the properties of the inhibitor of Tubularia, as described by Rose and 

 Rose (1941) and Tardent (1955), respectively. The inhibitors of the liver (Brues 

 et ah, 1940) and of the orbital gland (Teir, 1952) are heat-labile, while promotors 

 are more heat-stable (Marshak and Walker, 1945; Teir, 1952) though both stable 

 and labile components are demonstrable in embryo-extract (Fischer, 1948; Mar- 

 goliash and Doljanski, 1950; Harris, 1953). Both promotor (Teir, 1952) and in- 

 hibitor (Rose and Rose, 1941; Tardent, 1955) are water-soluble but there are 

 contradictory reports of the solubility-properties of the nerve-regeneration 

 promotor (p. 643) 



It is not clear at present how organ- or tissue-specific PI substances are related 

 to the complex of direct metabolic controls, by SH-compounds, by muco-protein 

 components, and probably by most active metabolites, though they presumably 

 act at a higher level, on the process as a whole. In this respect, at least, they would 

 be hormonal in nature. By contrast the direct metabolic controls are specific to 

 particular reactions and on the other hand are not specific to organ or tissue. It 

 would seem probable that the mucoprotein inhibitor of Balazs and Holmgren 

 belongs to this latter group. 



Lilerature p. 64/) 



