Ontogeny of Endocrine Correlation 



601 



of growth after hypophysectomy is associated 

 with concomitant arrested growth and di- 

 minished function of the adrenal cortex and 

 thyroid glands. Likewise, restoration of 

 growth to normal by hypophyseal adminis- 

 tration is accompanied by concomitant res- 

 toration of the growth and function of the 

 adrenal cortex and thyroid. This thus poses 

 the problem whether tadpole growth is the 

 result of multiple gland activity. 



Does thyroid removal affect the growth of 

 the anuran tadpole? If the anterior pituitary 

 alone is essential it might be expected that 

 the thyroidectomized tadpole would continue 

 to grow although metamorphosis would not 

 take place. In contrast to a distinct re- 

 tardation of growth rate in the pituitaryless 

 tadpole, the thyroidless tadpole, produced by 

 removal of the thyroid primordium shortly 

 after its formation, continues to grow, ul- 

 timately attaining a body size much in excess 

 of the normal control (Allen, '18; Hoskins 

 and Hoskins, '19). Concomitantly with the 

 increased growth of the body, the vertebral 

 skeleton continues to increase in size. Calci- 

 fication proceeds extensively, but little or no 

 ossification takes place. On the contrary, in 

 the hind limb growth of the skeleton prac- 

 tically ceases, and although calcification of 

 the cartilage proceeds the process of ossifica- 

 tion is much retarded (Terry, '18). More- 

 over, growth in body size may be augmented 

 by four times that of thyroidectomized con- 

 trols by intraperitoneal injections of bovine 

 anterior lobe extracts (Smith and Smith, 

 '23). The degree of growth is sufficiently 

 striking to suggest that the apparent growth- 

 promoting action of the anterior pituitary is 

 independent of thyroid activity. However, 

 the extent to which the increase in body 

 size may be attributed to excess growth 

 stimuli from the hypertrophied anterior 

 pituitary of the thyroidless tadpole or to a 

 supplementary injection of pituitary prin- 

 ciples, or to still other factors, is difficult to 

 assess for two main reasons: (1) The rate 

 of growth of thyroidless, pituitaryless, and 

 normal frog larvae on a similar dietary 

 regime may be nearly identical. (2) In thyro- 

 hypophysectomized tadpoles growth of the 

 body, although limited, nevertheless con- 

 tinues, body and hind limb growth keeping 

 pace with one another, indicating that fac- 

 tors other than hypophyseal or thyroid hor- 

 mones are concerned. Since, however, either 

 thyroid preparations or iodine administered 

 to tadpoles deprived of both glands or of 

 either one alone promptly arrests growth 

 with ensuing metamorphosis, it is clear that 



the thyroid or its active principle has an 

 antagonistic action to anterior pituitary. 



In summary, it appears that the anterior 

 pituitary has a growth-promoting action, 

 whereas the thyroid has an inhibitory action 

 on the processes of growth of the anuran 

 tadpole. This apparent contrasting action on 

 tadpole growth is difficult to interpret, since 

 as yet the evidence is neither adequate nor 

 critical. Moreover, the elucidation of their 

 action on growth is still further complicated 

 by the commonly overlooked fact that hypo- 

 physectomy affects not only the thyroid but 

 also the adrenal cortex of the tadpole. It is 

 now well established — for mammals, at least 

 — that the hormones of the adrenal cortex 

 participate in carbohydrate metabolism (in- 

 fluence on the rate of gluconeogenesis from 

 protein) . The possibility of a linkage between 

 the anterior pituitary, the thyroid, and the 

 adrenal cortex in regulating growth and 

 differentiation of the anuran tadpole must, 

 therefore, be recognized. Such a functional 

 interaction may in part be resolved by 

 analyzing the effects of purified growth 

 hormone both separately and in all possible 

 combinations with thyroxine, thyrotrophin, 

 ACTH, and adrenocortical hormones on the 

 growth of hypophysectomized, thyrodecto- 

 mized, and thyro-hypophysectomized tad- 

 poles. Also, the extent to which dietary 

 nvitrients play a role in tadpole growth needs 

 to be more precisely ascertained than here- 

 tofore. 



The role of the anterior pituitary in regu- 

 lating body growth has been most clearly 

 demonstrated in mammals, especially in the 

 actively growing postnatal rat, for which 

 the evidence is most complete and critical. 

 Complete removal of the anterior lobe from 

 young rats during the period of active 

 growth (usually 26 to 36 days after birth) 

 invariably results in cessation of over-all 

 body growth and leads to permanent dwarf- 

 ism as a consequence. Save for slight fluctua- 

 tions among individuals the size, weight, 

 and length remain stationary. Skeletal 

 growth is arrested. The growth stasis thus 

 displayed in pituitaryless rats is readily 

 broken at any time by daily homeo-implants 

 of anterior lobe or injections of growth 

 hormone preparations. Such treatment 

 quickly causes a resumption of growth, 

 which continues more or less normally. 



Undergrowth (cretinoid dwarfism) is like- 

 wise produced by the removal of the thyroid. 

 In rats dwarfed by thyroidectomy, growth is 

 induced by the administration of growth hor- 

 mone extracts. On the contrary, thyroid ad- 



