584 



Ontogeny of Endocrine Correlation 



the hormone in amounts insufficient to have 

 an activation effect via the vascular circula- 

 tion. 



Grafts of the anterior lobe from anuran 

 tadpoles of different ages vary in their 

 effectiveness in bringing about precocious 

 metamorphosis in host tadpoles of immature 

 stages. Anterior pituitaries from animals in 

 metamorphic climax are highly potent as 

 grafts in stimulating metamorphosis, whereas 

 those from donors before the onset of meta- 

 morphosis are impotent (Allen, '38). These 

 results may be interpreted as indicating that 

 the normal anterior pituitary undergoes a 

 sudden increase in the production of thyro- 

 trophic substance at the time of metamorpho- 

 sis (Etkin, '38). This marked change in 

 activity appears to be the primary stimulus 

 at metamorphosis, since it is known that the 

 receptor gland is responsive to the pituitary 

 long before the normal time of metamorpho- 

 sis. This peak is soon followed by a decline in 

 thyrotrophic activity, since grafts of glands 

 from tadpoles in stages beyond the more 

 active phases of metamorphosis give a re- 

 tarded response in premetamorphic tadpole 

 hosts. During the subsequent growth of the 

 young or juvenile frog no information is 

 available as to the time that thyrotrophic 

 activity of the anterior lobe again attains a 

 high level. It is highly potent in adult frogs 

 as measured by its capacity to induce pre- 

 cocious metamorphosis. 



Since the quantity of thyrotrophic sub- 

 stances is apparently low at first, it should 

 be expected that an excess number of anterior 

 pituitary grafts would produce a precocious 

 metamorphosis. In Rana sylvatica this ap- 

 pears to be the case (Etkin, '35). As grafts, 

 a single anterior pitviitary primordium is in- 

 sufficient; but three extra primordia (total 

 of four acting) are sufficient to induce meta- 

 morphosis in 7.8 ±1.4 days as compared 

 with 17.7 ± 0.6 days required for the un- 

 operated controls. Fvu-thermore, the animals 

 with four primordia are significantly smaller 

 than the controls at the time of metamorpho- 

 sis. Thus the difference in time required for 

 and maximum size attained at metamorpho- 

 sis give a rough measure of the quantity of 

 hormone produced. The results support the 

 interpretation that the anterior pituitary 

 primordium produces the hormone in small 

 quantities in the anuran embryo. 



Little or no information is available as to 

 whether the thyrotrophic substance is pro- 

 duced in increasing amounts during the 

 ontogeny of amniotes. As previously noted, 

 the presence of thyrotrophic activity of the 



anterior lobe of the fetal pig is indicated 

 near the time of birth but not earlier. The 

 experiments were designed to ascertain the 

 time of onset of secretory activity and not 

 the quantity of hormone produced. More re- 

 fined quantitative methods of extracting and 

 of bio-assay of the thyrotrophic hormone 

 from the anterior lobe from fetal and post- 

 fetal stages are needed in order to ascertain 

 the quantity necessary for thyroid activation 

 and consequent effects on the metabolism of 

 growth. 



Finally, the question is raised as to whether 

 the thyroid has a reciprocal action on the 

 anterior pituitary during ontogeny. Does 

 the thyroid hormone released into the blood 

 by the activated thyroid regulate or depress 

 the quantity of thyrotrophic substance pro- 

 duced or released by the anterior pituitary, 

 the trophic gland? Is the secretory output of 

 trophic and effector glands regulated by a 

 balance between the quantities of thyro- 

 trophic and thyroid hormone in the blood 

 circulation? That the thyroid has an effect 

 on the development of the anterior pituitary 

 is brought out by the study of thyroidecto- 

 mized anuran embryos (Hoskins and Hos- 

 kins, '19; Smith, '20). By removing the 

 thyroid primordium from embryos at an 

 early stage (/?. sylvatica embryos 5 to 8 mm. 

 in length) thyroidless larvae are obtained. 

 At the expected time of metamorphosis of 

 such tadpoles, the anterior lobe is definitely 

 larger and the number of acidophiles greater 

 than in control tadpoles of the same size 

 and age. The validity and significance of 

 these findings must await further investiga- 

 tion. The increase in number of acidophiles 

 is puzzling, in view of the fact that thyroid 

 removal in certain species of mammals dur- 

 ing postnatal life commonly leads to a de- 

 crease in number or complete loss of acido- 

 philes and an increase of basophiles in the 

 anterior lobe (Severinghaus, '37). 



A large body of evidence indicates in 

 general that thyrotrophic potency of the 

 anterior pituitary varies in different species 

 and within the same species at different 

 ages (or phases of reproductive activity). 

 Such potency changes, particularly those 

 following thyroidectomy, lend support to the 

 commonly accepted theory that a high level 

 of thyroid hormone suppresses the production 

 and release of the thyrotrophic substance and, 

 conversely, a low level of the thyroid hor- 

 mone stimulates the production and release of 

 thyrotrophic substances by the pituitary (for 

 a review of the evidence see Adams, '46). In 

 keeping with this theory is the significant 



