Ontogeny of Endocrine Correlation 



575 



principal lines of evidence (see Allen, '29 

 and '38, for details and citations to literature). 

 (1) The thyroid glands mvist be present for 

 the anterior pituitary to bring about meta- 

 morphosis. Implants or extracts of the ante- 

 rior pituitary even in excessive amounts fail 

 in the absence of the thyroid. (2) Colloid 

 secretion and accompanying metamorphosis 

 are restored in hypophysectomized tadpoles 

 by implants of the pars anterior of adult 

 frogs or by repeated intraperitoneal injections 

 of extracts of the anterior lobe of bovine 

 pituitary. The anterior pituitary is thus 

 clearly essential for thyroid activity. The 

 effective substance is regarded as a thyro- 

 trophic hormone from the specific nature of 

 the response, i.e., the effect is upon the thy- 

 roid gland, enabling it to store thyroglobulin 

 and to release its hormone. 



More recent studies likewise indicate for 

 the chick embryo that the anterior pituitary 

 exerts a trophic effect on the thyroid glands 

 (Fugo, '40; Martindale, '41). Following re- 

 moval of the prosencephalic portion of the 

 head (thereby excluding both primordia of 

 the pituitary) of 33- to 38-hour embryos, 

 thyroid development during the latter half 

 of the incubation period is retarded. The 

 follicles are relatively few in number, small 

 in size, and contain little or no colloid in 

 contrast to normal thyroids of equivalent age 

 where the follicles are numerous, well 

 formed, and contain an abundance of colloid. 

 That such a change can be attributed to the 

 absence of a trophic effect is indicated by 

 the results of grafting the thyroid glands 

 from a pitviitaryless embryo of 12 days to the 

 chorio-allantois of 8-day normal and pitui- 

 taryless host chicks. After a period of 4 to 

 10 days of growth on the normal host the 

 thyroid graft shows distinct follicles, which 

 in degree of development and quantity of 

 colloid are characteristic of the host age, 

 whereas on the pituitaryless host the follicles, 

 if formed at all, are very small and colloid 

 is absent or scanty. In either case the thyroid 

 graft is structurally similar to the host thy- 

 roid. From this striking difference in re- 

 sponse of the thyroids it is inferred that the 

 anterior pituitary of the normal host exerts a 

 trophic effect on the thyroid graft through 

 the extraembryonic circulatory blood vessels. 



TIME RELATIONS IN DEVELOPMENT 

 OF SECRETORY ACTIVITY 



The foregoing analysis showing that the 

 secretion of thyrotrophic substance by the 

 anterior pituitary is essential for the normal 



histogenesis and function of the thyroid and 

 operates via the vascular circulation next 

 poses the problem of the time relations in 

 the assumption of secretory activity of these 

 glands. In general, the functional tests for 

 thyroid activity of embryonic glands from 

 variovis vertebrates (see Table 27) indicate 

 a fairly close correlation between the time 

 of initial colloid accvimulation and the ca- 

 pacity to induce metamorphosis in frog tad- 

 poles. During progress toward metamorpho- 

 sis in anurans the follicles progressively in- 

 crease in size and in the accumulation of 

 colloid within them. These changes with age 

 are apparently accompanied by an increase 

 of hormonic efficiency. For example, accord- 

 ing to Swingle ('23) thyroids, when tested 

 for capacity to induce metamorphic changes 

 in immature host larvae, have a much greater 

 physiological activity at the time of meta- 

 morphosis than during earlier larval stages. 

 Prior to the phase of colloid storage the thy- 

 roid has little or no capacity to induce meta- 

 morphosis. 



At what time in thyroid development does 

 iodine or its compounds begin to accumu- 

 late? In the frog embryo (10 mm.), the 

 rat fetus (18- to 19-day), the rabbit fetus (20- 

 day), and the chick embryo (7-day), the 

 thyroid has the capacity to accumulate 

 radioactive inorganic iodine as revealed by 

 radioautographs or by Geiger counts (Gorb- 

 man and Evans, '41, '43; Jost et al., '49; 

 Wollman and Zwilling, '53). Although prob- 

 ably present earlier, measurable amounts of 

 iodine are first detected by microchemical 

 analysis in bovine fetal thyroids at 60 days 

 of age (Wolff et al., '49) and in the thyroid 

 of pig fetuses of 7 to 8 cm. (46 to 50 days of 

 age) according to Rankin ('41). In all of 

 these cases, iodine is present at least in 

 detectable amounts at a time prior to the 

 onset of formation of follicles. In the calf 

 fetus organic iodine compounds are present 

 in the thyroid before intracellular colloid or 

 follicle formation can be detected histologi- 

 cally (Koneff et al., '49). It is apparent, there- 

 fore, that prior to follicle formation the cords 

 or group of epithelial cells of the thyroid 

 already have the capacity to select iodine 

 from the common blood pool of the embryo. 

 The time that the cells of the thyroid acquire 

 a specific selective affinity for iodine is a 

 problem which needs further investigation 

 (see Table 27). 



Following the initial accumulation in rel- 

 atively small amounts, a progressive in- 

 crease in thyroid iodine ensues. Although, as 

 noted above, inorganic iodine is first detected 



