654 



Metamorphosis 



CONTROL OF PITUITARY ACTIVITY 

 IN AMPHIBIANS 



The evidence indicates that the thyroid 

 gland lies ready, so to speak, to respond to 

 pituitary stimulation at all times from the pri- 

 mordial stage onward. One experimental re- 

 sult leading to this conclusion is the fact that 

 when thyroid and pituitary primordia are 

 brought close together in the tail-bud stage 

 of the frog the thyroid is activated within 

 a few days and an extremely precocious 

 metamorphosis is induced (Etkin, '36b, '39). 

 The act of transplantation itself has no in- 

 fluence, since transplants to other localities 

 lead to no precocity (Hoskins and Hoskins, 

 '19a; Etkin, '39). The thyroid activation 

 must therefore be a resvilt of locally concen- 

 trated thyrotrophic pituitary hormone. An- 

 other indication of the dependence of thyroid 

 activation upon the time of arrival of the 

 pituitary stimulus rather than upon any 

 change in the thyroid itself is shown by the 

 fact that the introduction of additional thy- 

 roid primordia (not into the vicinity of the 

 pituitary) does not influence the time of 

 metamorphosis of the host (Allen, '30; Choi, 

 '32). 



In contrast to the thyroid the pituitary is 

 independent of any other organ of the body 

 for its activation. This conclusion is based 

 on experiments in the transplantation of the 

 pituitary primordium (Etkin, '38). When 

 the primordium is removed from its normal 

 site and transplanted to another part of the 

 body, the animal undergoes metamorphosis. 

 But this metamorphosis is generally delayed 

 in its onset and protected in its execvition. 

 This is interpreted as indicating that the 

 grafted pituitary generally develops its func- 

 tion more slowly than normal. Unlike the 

 thyroid, its function depends upon its devel- 

 opmental rate, which is somewhat inhibited 

 by the experimental interference, rather than 

 upon a hormonal stimulus which would, of 

 course, reach it at the same time wherever 

 it is located. 



The precocious activation of the thyroid 

 primordium when placed close to the pitui- 

 tary primordium, as mentioned above, indi- 

 cates that the production of thyrotrophic 

 hormone begins very early. That the thyroid- 

 stimulating field existing around the pitui- 

 tary primordium is due to the same hormone 

 as that which later normally stimulates 

 thyroid development is indicated by the find- 

 ing that histologically differentiated thyroids 

 respond to the thyrotrophic field. Presumably 

 the amount of hormone produced by the pri- 



mordium is so small as to be ineffectual 

 when carried by the circulation. Before cir- 

 culation is established, however, it appears 

 to accumulate arovmd the pituitary primor- 

 dium in concentration sufficient to produce 

 an effective thyrotrophic field. 



As to the pattern of post-primordial devel- 

 opment of function in the pituitary, little is 

 known. Using implantation techniques In- 

 gram ('29a) found that it took 15 to 20 

 pituitaries from tadpoles at the beginning of 

 metamorphosis to equal the effect of three 

 adult frog pituitaries. This indicates, con- 

 sidering the difference in size of the glands 

 concerned (for which exact figures are not 

 available), that the hormone is present in 

 fair quantity in the tadpole pituitary. It 

 must be supposed, therefore, that hormone 

 production begins in the primordium and 

 increases at an unknown rate to reach a high 

 level at the beginning of metamorphosis. 

 Whether the subsequent increase in thyroid 

 activity to the climax of metamorphosis and 

 the eventual cessation of thyroid activity at 

 the close of metamorphosis are paralleled by 

 corresponding changes in the activity of the 

 pituitary is not known. 



As seen above, the failure of the axolotl 

 to metamorphose is not due to insensitivity 

 of the tissues to thyroid hormone or of the 

 thyroid to pituitary stimulation. It must 

 therefore rest somehow on the failure of the 

 pituitary to become active. Bytinsky-Salz 

 ('35) explored this problem by exchanging 

 hypophyseal rudiments between the axolotl 

 {Amblystoma mexicanum) and a variety of 

 amblystoma {A. tigrinum) which metamor- 

 phoses normally. He found that the meta- 

 morphic response of the host was that char- 

 acteristic of the host species, not of the 

 pituitary-donor type. This he interpreted 

 (contrary to the conclusion stated above) as 

 indicating that the pituitary is not function- 

 ally self-differentiating but is dependent 

 upon some controlling factor elsewhere in 

 the body for its own activation. However, 

 the writer does not find the evidence pre- 

 sented to be convincing. The grafts were 

 made in the orthotopic position, being made 

 to replace the animal's own prospective 

 pituitary area which had been removed. It 

 is therefore impossible to be sure that the 

 pituitary which developed in the animal 

 came from the graft rather than by regen- 

 eration of the host's own tissues. This criti- 

 cism is especially pertinent since hypophy- 

 sectomies similarly carried out by Blount 

 ('32) yielded a high proportion of regener- 

 ated glands. 



