Ontogeny of Endocrine Correlation 



583 



of basophiles greatly predominates. During 

 successively later stages the acidophile popu- 

 lation gradually increases until the 160 to 

 170 mm. stage, at which time a marked rise 

 in their nvmiber is exhibited. Although at 

 this time the acidophile population is mark- 

 edly increased, the functional test as noted 

 above does not indicate thyrotrophic activity. 

 It is possible that although the thyrotrophic 

 substance is produced by the anterior lobe it 

 is not present in sufficient quantity in the 

 extracts thereof to elicit a positive response 

 in hypophysectomized tadpoles. By this 

 method of bio-assay the hormone appears to 

 be present in svifficient quantities only near 

 the time of birth. Nevertheless, its presence 

 as early as 90 mm. is indicated, since at that 

 stage but not earlier (1) minute droplets of 

 colloid appear within follicles of the thyroid 

 and (2) thyroid extracts stimulate metamor- 

 phosis in the hypophysectomized tadpole 

 (Rumph and Smith, '26). It must be recog- 

 nized, however, that (a) the thyroid may 

 attain an initial fvmctional state independ- 

 ently of thyrotrophic secretions, {b) the bio- 

 assay method is not sufficiently sensitive for 

 detecting minute quantities of thyrotrophic 

 hormone, and (c) the hormone may be sup- 

 plied to the fetus by the mother. The evidence 

 is inadequate for deciding whether one type 

 of cell or the other is related to the produc- 

 tion of thyrotrophin in the pig fetus. 



In the chick embryo a fairly close correla- 

 tion exists between the time of differentiation 

 of the thyroid and of the cell types of the 

 anterior pituitary. The thyroid begins to 

 store colloid in follicles on the tenth day 

 (Hopkins, '35), at which time the acido- 

 philes are first apparent in the anterior lobe. 

 The acidophiles gradually increase in num- 

 ber with advance in age, becoming the 

 dominant type of cell by the eighteenth day 

 (Rahn, '39) or by the third day after hatch- 

 ing (Payne, '46). Although relatively few 

 basophile-like cells appear to be present as 

 early as the twelfth day, they do not attain 

 a fully differentiated state until about ten 

 days or more after hatching. In the chick 

 the presence of acidophiles and basophile-like 

 cells seems to precede by one day the onset 

 of thyrotrophic secretion, as is revealed by 

 grafting thyroid glands from hypophysecto- 

 mized donors to the chorio-allantois of nor- 

 mal and hypophysectomized chick hosts. 

 From the differences in thyroid response 

 given it may be inferred that the thyro- 

 trophic hormone is produced in small yet 

 significant amounts as early as the eleventh 

 day and in still greater amounts from the 



twelfth to the eighteenth day of incubation 

 (Martindale, '41). 



To summarize, it becomes apparent on the 

 basis of fvmctional tests that the anterior 

 pituitary during embryonic development 

 produces a thyrotrophic hormone. Regardless 

 of whether basophiles or acidophiles arise 

 first, a predominance of acidophiles usually 

 occurs according to the majority of investi- 

 gators during some phase of pituitary devel- 

 opment of the growing embryo. Although it 

 is difficult to relate the specific cells to 

 specific secretions, the body of evidence sug- 

 gests that the acidophiles may be associated 

 with the production of the thyrotrophic 

 hormone and, as will be seen below, of the 

 growth hormone as well. 



Since it is evident that a thyrotrophic sub- 

 stance is produced sooner or later by the 

 developing anterior pituitary, it is important 

 to know whether the hormone content in- 

 creases quantitatively with developmental 

 age. This appears to be the case, as several 

 lines of evidence indicate. From a study of 

 the effects of approximating the primordia 

 of the anterior pituitary and thyroid in 

 anuran embryos, Etkin ('39) concluded that 

 a "field of thyrotrophic substance" surrounds 

 the normal pituitary in quite early stages of 

 development. The activation effect on the 

 thyroid is limited in its range. As noted 

 above, an extra thyroid grafted near the 

 pituitary of a host is activated, whereas the 

 thyroid of the host is not. This suggests that 

 the manner of dispersal of the thyrotrophic 

 substance is by diffusion through the tissues 

 rather than through the blood stream.* 

 Furthermore, it is probable that the anterior 

 pituitary at the stages tested is producing 



* The concept of a direct and local action of hor- 

 mones in actuating the expression of the intrinsic 

 potentialities of endocrine receptor glands and tis- 

 sues is well substantiated by three recent discov- 

 eries. (1) Sex hormones of an embryonic gonad in 

 contact with another one of opposite sex constitu- 

 tion or with a terminal sex receptor elicit specific 

 responses of the tissue components in accordance 

 with their pre-existing reaction capacities (for a 

 more extensive treatment of the subject see p. 594). 

 (2) Hormones from a thyroid graft act locally by 

 direct contact in accelerating metamorphic events 

 in the neuronal elements of the hindbrain of the 

 anuran tadpole (Weiss and Rossetti, '51). (3) Hor- 

 mones from fragments of the anterior pituitary 

 (31/^-month cockerel) cultivated for 9 days in vitro 

 in close contact with a thyroid gland of the pre- 

 follicular stage (S^^-day chick embryo) greatly 

 stimulate the formation of intracellular colloid 

 droplets in the parenchymal tissue of the thyroid; 

 follicles, however, fail to form (Gaillard, '53). 



