582 



Ontogeny of Endocrine Correlation 



capacity of the fetal thyroid gland to store 

 iodine and its compounds. 



The question next arises as to the time 

 when the thyroid primordium in the course 

 of its development is responsive to the thyro- 

 trophic hormone. Shortly before and at the 

 time of follicle formation the thyroid is 

 known to be responsive to anterior lobe 

 stimulation. That it behaves as an effector 

 organ long before colloid storage begins is 

 brought out in frog embryos by grafting the 

 primordium of either the thyroid or the 

 anterior pituitary so that the two are in 

 closer proximity than in their normal sites 

 (Etkin, '39). Irrespective of whether one or 

 the other gland is shifted or an extra gland 

 grafted, such proximity leads to a precocious 

 activation of the thyroid with consequent 

 precocious metamorphosis. There is no pre- 

 cocity if either gland is grafted to a site 

 outside the neighborhood of the other, i.e., 

 apparently when the thyroid is beyond the 

 range of influence of the anterior lobe (see p. 

 583). Furthermore, an extra thyroid grafted 

 near the pituitary is activated, whereas the 

 host thyroid at its normal site is not. The acti- 

 vation of the thyroid is first visibly evident at 

 approximately seven days after the operation, 

 at which time the follicles are greatly en- 

 larged and contain abundant colloid, con- 

 trasting with the control thyroid where these 

 processes are much less advanced. The acti- 

 vated gland shows a marked increase in size 

 (volume), reaching at 19 days a size over 

 twenty times that of the normal thyroid. 

 It is evident, therefore, that the thyroid 

 primordium is in a responsive state for a 

 considerable length of time prior to its normal 

 histological differentiation and is apparently 

 as responsive as the gland in which follicle 

 formation is about to begin or has begun. 



At what time in the course of development 

 of the anterior lobe does the secretion of 

 thyrotrophic substance begin? Is its time of 

 onset prior to or coincident with the histo- 

 logical differentiation of cell types? The early 

 responsiveness of the thyroid analyzed above 

 indicates that the anterior pituitary is con- 

 currently active in producing a thyrotrophic 

 substance. Since the activation of a thyroid 

 in proximity to an anterior lobe is similar in 

 natiire to activation by the thyrotrophic 

 hormone known to be produced at later 

 stages, it is inferred that the production of 

 the hormone begins very early in pituitary 

 development of anurans. It apparently be- 

 gins not later than seven days after the tail- 

 bud stage, which is long before it is func- 

 tionally effective in normal anuran meta- 



morphosis (Etkin, '39). Surely at the tail- 

 bud stage the cells of the hypophyseal pri- 

 mordium, which has just invaginated to a 

 position below the infundibulum, are not 

 visibly differentiated into cell types (so 

 reported for R. pipiens by Kleinholz, '40). 

 The cell types apparently differentiate con- 

 siderably later. According to Kerr ('39), 

 whose study of histogenesis of the anterior 

 lobe in relation to the thyroid in the anurans 

 (R. temporaria and Bufo bufo) is the most 

 detailed and complete, the acidophiles ap- 

 pear prior to metamorphosis, i.e., at the stage 

 when the larvae are first completely free- 

 swimming (11 to 13 mm. in length), whereas 

 the basophiles first appear during the most 

 active period of metamorphosis, i.e., of rapid 

 growth of hind legs, appearance of fore-legs, 

 and tail absorption. Furthermore, the histo- 

 logical differentiation of acidophiles and the 

 first occurrence of minute droplets of colloid 

 in the thyroid coincide in time. This, coupled 

 with a steady increase in the number of 

 acidophiles and in the amount of colloid 

 during the early stages up to the beginning 

 of rapid hind-leg growth and with the ab- 

 sence of basophiles, shows a close corres- 

 pondence between acidophiles and thyroid 

 activity. Thus Kerr was led to infer that 

 thyrotrophic fimction and general body 

 growth as well are associated with the acido- 

 philes. 



In the amniotes but few attempts have been 

 made to correlate the initiation of thyro- 

 trophic activity with the histogenesis of the 

 anterior lobe. Of interest here is the pioneer 

 work of Rumph and Smith ('26). These in- 

 vestigators reported that intraperitoneal in- 

 jections of extracts of the anterior pituitary 

 from fetal pigs of 140 mm. and 160 mm. 

 stages fail to call forth a response in hypo- 

 physectomized frog tadpoles. However, at 

 260 to 280 mm. stages (near time of birth) 

 a definite although slight response is elicited 

 as indicated by a clear-cut stimulation of 

 hind-limb growth and som^e activation of 

 the thyroid. This capacity to evoke meta- 

 morphic changes appeared to be correlated 

 with the time (260 mm. stage) in histogenesis 

 of the cell types that the acidophiles became 

 nearly as numerous as in the adult pig gland. 

 (See Table 27.) 



However, that the acidophiles have a spe- 

 cific functional significance must be ques- 

 tioned in the light of later detailed studies 

 on the cytological differentiation of the ante- 

 rior pituitary in the fetal pig. Nelson ('33) 

 reports that, although acidophiles are present 

 at the 70 to 100 mm. stages, the population 



