Metamorphosis 



635 



lated between the absence of the pulmonary 

 arch and neoteny. The results may possibly 

 be explained by secondary effects which in- 

 fluence tissue sensitivity. 



It may be concluded on the basis of the 

 evidence summarized in this section that 

 the thyroid through its hormone is the pri- 

 mary determinant of metamorphic transfor- 

 mation in amphibians. Except for the 

 hypophysis, which acts through the thy- 

 roid as discussed below, no other organ is 

 known to exert significant control over the 

 process. The evidence implies, though it 

 does not definitely prove, that the thyroid 

 hormone acts directly without the media- 

 tion of other organs in the initiation of 

 metamorphosis. 



ROLE OF HYPOPHYSIS 



Hypophysectomy in amphibians prevents 

 metamorphosis. This was first found by Adler 

 ('14), who hypophysectomized tadpoles by 

 cautery. He secured a few survivors of this 

 drastic operation and these showed, among 

 other effects, a failure of metamorphosis. 

 However, the relation of the hypophysis to 

 metamorphosis was not satisfactorily clari- 

 fied until Allen ('16) and Smith ('16) inde- 

 pendently developed the techniqvie of re- 

 moving the primordium of the pituitary 

 from the frog embryo (Fig. 219). These 

 investigators found that such hypophysecto- 

 mized tadpoles remain in the larval condition 

 indefinitely. Their rate of growth is retarded 

 but this does not account for the absence of 

 metamorphosis, since the animals may even- 

 tually attain or even exceed full size. The 

 development of the hypophysectomized tad- 

 pole parallels that of thyroidectomized ani- 

 mals. The hind legs in the two types, for 

 example, develop to the same degree (Allen, 

 '17). These findings have been extensively 

 confirmed (see, for example, Blount, '35; 

 Etkin, '38). 



The explanation of the manner of action 

 of the anterior pituitary was soon made 

 apparent by studies of Smith (see summary 

 in Smith, '20) and Allen ('32a). They 

 showed that, in the absence of the anterior 

 pituitary, the thyroid remains very small 

 and poorly developed. It never undergoes 

 the great spurt of growth nor does it give 

 the histological evidence of activation that 

 characterizes the metamorphic period in the 

 normal animal. It is therefore apparent that 

 the anterior pituitary is necessary for the 

 activation of the thyroid and that its influ- 

 ence on metamorphosis is to be accounted 



for by its control of the thyroid rather than 

 by a direct effect on the tissues. 



This control of the thyroid by the anterior 

 pituitary is effected by a thyrotrophic hor- 

 mone produced in the anterior lobe of the 

 gland. This was demonstrated by experi- 

 ments with implants, extracts and trans- 

 plants of the hypophysis in the major groups 

 of vertebrates. Only the evidence relating 

 to the activation of the thyroid in metamor- 

 phosis will be considered here. 



Transplanted anterior lobes from adult 

 amphibians are effective in inducing meta- 

 morphosis in normal and hypophysectomized 

 but not in thyroidectomized larvae. The 



Fig. 219. Sagittal section of frog embryo at early 

 tail-bud stage. Hypophyseal primordium shown in 

 black is removable through slit made along broken 

 line. (After Allen, '29a.) 



thyroids of normal and hypophysectomized 

 host animals receiving such implants show 

 clear histological evidence of activation 

 (Allen, '27; Grant, '31). Allen ('31) also 

 fovmd that pituitaries from tadpoles in meta- 

 morphosis were effective but those from 

 pre-metamorphic animals were not. Evidence 

 of the development of thyrotrophic function 

 in hypophyses transplanted as rudiments in 

 embryonic stages was found in tadpoles 

 (Atwell, '37; Etkin, '35b) and in Amblys- 

 toma (Blount, '35; Atwell and Taft, '40). 

 Etkin ('38) obtained cases in which such 

 transplanted primordia attained fvdl func- 

 tional activity in hypophysectomized host 

 tadpoles. 



Although the first studies with tissue ex- 

 tracts gave conflicting results (see Allen, 

 '38), today it is clear that thyrotrophic 

 preparations derived from the pituitary of 

 various animals are effective in amphibian 

 metamorphosis but only in the presence of 

 the thyroid, which becomes activated by 

 such extracts (Figge and Uhlenhuth, '33; 

 Krichesky, '34; Atwell, '35). Comparative 

 assays of the anterior pituitary of various 

 animals showed the pituitary of the frog to 

 be especially rich in thyrotrophins (Gorb- 



