Ontogeny of Endocrine Correlation 



611 



the thyroid barely begins to store thyroglob- 

 ulin in follicles on the ninth day. Seem- 

 ingly, during this phase the processes 

 concerned with the acciimulation of carbo- 

 hydrate in the liver and blood are to a 

 high degree, if not entirely, independent of 

 hormonal activity. These processes, although 

 of obscure nature, are in some manner partly 

 linked with the glycogenic and glycogeno- 

 lytic functions of the yolk-sac membrane 

 (in this organ glycogen attains maximum 

 concentration at 8 days, whence it diminishes 

 to a lower level by the twelfth day according 

 to Zwilling, '51). 



The period from about the tenth through 

 the thirteenth day is characterized by a 

 concatenation of events of a widely diverse 

 nature. Such an impressive array of events 

 as are listed in the chart (many are not 

 listed) clearly suggests the onset of chemical 

 integration. Apparently the glands and or- 

 gans have become correlated functionally 

 with each other in a chainlike manner 

 through hormones and other humoral sub- 

 stances transported in the blood vascular 

 circulation. Since significant changes in car- 

 bohydrate accumulation take place during 

 this period in normal and in experimentally 

 treated embryos, it may be inferred that 

 the hormonal mechanisms which contribute 

 to the homeostatic regulation of blood sugar 

 are beginning to unfold. 



From approximately the fourteenth day 

 to the time of hatching is a period of appar- 

 ent maturation of functional activities pre- 

 viously set in operation. A strengthening and 

 extension of functional interlocking of the 

 glands via the hormones and other humoral 

 substances is postulated on the basis of the 

 progressive increases in specific glandular 

 tissue, in quantity of glandular secretions, 

 and in quantities of sugar and certain other 

 constituents of the blood. 



In conclusion, the over-all problem of the 

 development of the functional activity of 

 the islets and the mechanisms of regulation 

 of insulin secretion into the blood is only 

 beginning to take shape. In perspective the 

 foundations have been laid for a compre- 

 hensive analytical attack on the problem 

 which should be pressed at an increasing 

 tempo. 



PARATHYROID GLANDS 



Although the functional role of the para- 

 thyroids of the adult mammal has been 

 reasonably well worked out (Greep, '48), 

 relatively little attention has been directed 



to the problem of the development of their 

 functional activity. In the past practically 

 all studies have been directed toward an 

 elucidation of the site of origin and morpho- 

 genesis of the parathyroids. Since these 

 glands arise typically in four different loci, 

 are extremely small, and are intimately 

 associated with the thymus and thyroid, 

 studies on the effects of their experimental 

 removal in the embryo are fraught with un- 

 usual difficulty. 



As an indispensable background for imder- 

 standing the ftmctional development of the 

 parathyroids, the main sequential steps in 

 their morphogenesis, histogenesis, and 

 growth will be examined. These processes 

 have been most carefully studied in the 

 developing human embryo by Norris ('37). 

 It is now generally agreed that these glands, 

 commonly four in number, arise early in 

 development (8 mm. embryo of man) as 

 four localized proliferations of entodermal 

 cells of the dorsal-lateral wall of the third 

 and fourth pharyngeal pouches. Each local- 

 ized proliferation takes on the form of a 

 solid bud, which gradually becomes detached 

 from the pouch, whereupon it assumes a 

 globular shape, only later in fetal develop- 

 ment attaining its definitive, more or less 

 elliptical, form. Although arising from sep- 

 arate pouches, there are no essential differ- 

 ences in morphogenesis, in histogenesis, or 

 in rate of growth of the four parathyroid 

 primordia. 



The chief or principal cell (or variants 

 thereof) appears to be the only cell type to 

 arise during embryonic life and, moreover, 

 is the only type of cell found in postnatal 

 life in most animals; the so-called oxyphile 

 cell (possibly representing a transitional or 

 regenerative phase of the chief cell) is "an 

 inconstant component appearing in the hu- 

 man gland only after childhood" (Greep, 

 '48). Singularly, there is no clear C5^ological 

 evidence of secretory activity in the chief 

 cells of the adult glands, even though the 

 physiological evidence for endocrine secre- 

 tion is irrefutable. 



During the course of morphogenesis, histo- 

 genesis, and growth of the parathyroids of 

 man three main points stand out as possible 

 indices of ftmctional activity: (1) clear chief 

 cells, the essential elements of the glands in 

 postnatal life, are present in the early pri- 

 mordia of the parathyroids (9-mm. embryo) 

 and at all subsequent stages in their develop- 

 ment during fetal life; (2) the growth in- 

 crement of the glands (mainly by increase 

 in number of chief cells) per unit length 



