634 



Metamorphosis 



metamorphose is due to lack of tissue sensi- 

 tivity rather than to failure of glandular 

 activity. But occasional cases of neoteny in 

 species normally metamorphosing have been 

 correlated with pathological thyroid deficien- 

 cies (Bolten, '26). In the axolotl, a neotenous 

 form of Amblystoma, Uhlenhvith ('27) found 

 a gland whose structvu-e indicates that the 

 hormone is produced and stored but not 

 released to the circulation. 



It can thus be seen that the relation of 

 thyroid to metamorphosis has been ap- 

 proached from many different aspects with 

 concordant results. The evidence shows 

 clearly that the thyroid produces a hormone 

 which serves as the stimulvis precipitating 

 metamorphosis. 



The thyroid is unique in its relationship 

 to metamorphosis. Many organs, particularly 

 endocrine glands, have been studied in re- 

 lation to metamorphosis but none, with the 

 exception of the anterior lobe of the hypoph- 

 ysis which will be discussed below, has 

 been found to play any but a subsidiary role. 

 In the initial experiments by which Guder- 

 natsch opened this field of enquiry (Guder- 

 natsch, '12) the results of feeding with thy- 

 mus, adrenal, testis, ovary, spleen, liver, 

 pancreas and muscle were reported. None 

 of these accelerated metamorphosis. The 

 thymus diet seemed to delay this process, 

 presimiably because of its low iodine content 

 (see below). These results on the general 

 ineffectiveness of other organs were con- 

 firmed in regard to feeding by Abderhalden 

 ('15) and Hegner ('22). Injection and im- 

 plantation techniques with non-thyroid sub- 

 stances have likewise yielded negative re- 

 sults. Ovarian and testis implants are without 

 effect (Tutajew and Philippawa, '31), as 

 are insulin (Abderhalden, '24) and adrenal 

 implants when administered by themselves 

 (Woitkewitsch, '37). The pars intermedia 

 and pars nervosa of the hypophysis are like- 

 wise without effects on metamorphosis when 

 administered as implants (Swingle, '21; 

 Blount, '32; Etkin, '38). Salamandra has been 

 found to be capable of metamorphosis when 

 deprived of spinal cord and spinal ganglia 

 (Wintrebert, '06). 



In an often quoted work, Gutman ('26) 

 claimed to have metamorphosed young spec- 

 imens of the permanently neotenous urodele, 

 Necturus maculosus, by means of injections of 

 both thyroxine and adrenaline. This has not 

 been confirmed. Many observers, on the 

 contrary, have noted that various tissues of 

 larval amphibians may show considerable 

 reduction in volume under unfavorable en- 



vironmental conditions and yet recover com- 

 pletely on return to normal (Hoskins and 

 Hoskins, '19a; Noble, '24). Gutman's con- 

 clusion cannot be accepted, therefore, as being 

 a specific thyroid effect until confirmed by 

 fully controlled experiments. Attempts by the 

 writer to repeat Gutman's experiment failed 

 because the gills of the controls as well as 

 the experimentals showed considerable reduc- 

 tion under the laboratory conditions. 



An extensive literature exists on the rela- 

 tion of iodine to the thyroid hormone. Since 

 such work is concerned primarily with the 

 biochemical nature of thyroid secretions, de- 

 tails need not be considered here (Allen, '38; 

 Means, '48). Consideration of certain aspects 

 of the relation of thyroid activity to iodine, 

 however, is essential to an understanding of 

 the relation of thyroid to metamorphosis. 



The thyroid hormone contains iodine and 

 therefore cannot be synthesized by the ani- 

 mal body in the absence of this element 

 from the diet. Nearly all iodine that enters 

 the body is normally quickly concentrated 

 in the thyroid. Amphibia raised under 

 iodine-free conditions fail to metamorphose 

 (Uhlenhuth, '19; Lynn and Brambel, '35). 

 Contrariwise, the injection or implantation 

 of iodine can induce metamorphosis of am- 

 phibians even in the absence of the thyroid 

 gland (Swingle, '19; Ingram, '29b). We must 

 therefore suppose that, though iodine is 

 noi-mally metabolized through the thyroid 

 gland, the iodization of amino acids or 

 proteins can also take place elsewhere in the 

 body and can lead to the production of effec- 

 tive metamorphic stimulants. This interpre- 

 tation is made plausible by the fact that 

 proteins can readily be iodized by chemical 

 methods in vitro to yield thyro-active sub- 

 stances (Lerman and Salter, '39). 



Figge ('30, '34) found that ligation of the 

 pulmonary aortic arch in Amblystoma larvae 

 inhibits the subsequent metamorphosis of 

 these animals and decreases the effectiveness 

 of thyroid substance on them. This result 

 was attributed by him to the decrease in 

 oxygenation of the blood through the elim- 

 ination of the pulmonary circulation. He 

 ascribed an important role in the evolution 

 of the metamorphic mechanism to changes 

 in pulmonary circulation. However, Garber 

 ('30), working with Amblystoma, and Helff 

 ('31b) on Rana found that larvae deprived 

 of their lungs metamorphose normally and 

 respond in the usual way to thyroid stimu- 

 lation. McMullen ('38) made a comparative 

 study of the aortic arches of various urodeles 

 and found no correlation such as Figge postu- 



