The Mechanisms of Senescence 



probably through a negative feedback system from the level of 

 protein anabolism. It is particularly interesting to notice that 

 acromegalic symptoms (McCullagh and Renshaw, 1934) or 

 frank gigantism (Joedicke, 1919) are occasional sequels to 

 castration in males — so, however, are polyuria and diabetes 

 insipidus (Hamilton, 1948). The puberal growth phase in girls 

 appears to be largely of adrenal origin, since the growth- 

 promoting effects of oestrogens and of progesterone are less 

 marked, except in the promotion of Ca and P0 4 retention, 

 than those of androgens (Kinsell, 1953). It is generally held that 

 thyroxin potentiates the action of pituitary growth hormone in 

 mammals (Evans, Simpson and Pencharz, 1939; Scow and 

 Marx, 1945) during the prepuberal phase, as well as hastening 

 differentiation. This does not appear to be the case in anurans, 

 where thiouracil produces pseudogigantism, and a balance 

 between thyroid and pituitary has been postulated (Steinmetz, 

 1954), one evoking differentiation and the other growth and a 

 'juvenile' condition. 



This picture, which requires considerable amplification, 

 accords reasonably well with the known effects of various endo- 

 crine deficiencies in producing dwarfism or gigantism in man. 

 To some extent the appearance of the puberal cycle curtails the 

 prepuberal by inducing bone maturation. Epiphyseal union and 

 the change-over to the puberal phase of growth are delayed by 

 administration of growth hormone (Freud, Levie and Kroon, 

 1939), as they are in natural gigantism. On the other hand, 

 abolition of the whole gonadal influence by prepuberal castra- 

 tion has, at least, no gross effect on the life-span. Here again 

 the analogy to Edlen's findings in Daphnia is remarkably 

 close. 



Various workers have suggested that mammalian senescence 

 'is' (or involves) the decline of growth hormone production, 

 and that it 'is' (or involves) the long-term effect of the pituitary 

 gonadotrophin on non-gonadal tissues. Insofar as senescence 

 results from differentiation, this is doubtless true, but the experi- 

 mental question is rather this — to what extent can the adminis- 

 tration of one or more 'anabolic' hormones affect the power of 

 continued homoeostasis in adult animals? It is possible that the 

 growth hormone itself may be the 'juvenile hormone' of the 



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