Ontogeny of Endocrine Correlation 



613 



riety of conditions, chief of which are the 

 function of the parathyroids, the availability 

 of mobilizable calcium, and calcium utili- 

 zation. 



It might be expected on theoretical 

 grounds that the maintenance of calcium and 

 phosphate in the fetal blood in concentrations 

 above those in the mother is in some way 

 related to active deposition of those calcium 

 salts characteristic of developing bone. In 

 the albino rat active bone formation is in 

 progress during the latter third of the ges- 

 tation period (Strong, '25). Ossification is 

 initiated in a limited number of skeletal 

 elements (first in the clavicle) on the 17± 

 day. During subsequent days the mmiber of 

 such elements with beginning ossification 

 rapidly increases, reaching a peak near term 

 (21 days), when most of the bones of the 

 fetus exhibit ossification centers. Obviously 

 calcium and phosphorus are being utilized 

 in increasing amounts as the number of 

 ossifying bones increases. Although the con- 

 centrations of calcium and phosphorus in 

 the blood are known to be high at term, the 

 amounts present at earlier stages have not 

 yet been determined. Whether the concentra- 

 tion of these substances in the blood increases 

 concomitantly with the progressive increases 

 in the calcification of cartilage and of 

 periosteal bone would be of interest. 



Although calcium and phosphate occur 

 in fetal blood in concentrations above those 

 actually essential to the process of ossifica- 

 tion, the rate of their utilization is appar- 

 ently determined by the developing skeletal 

 elements. Two main lines of evidence may 

 be cited to show that the individual elements 

 of the vertebrate skeleton differ among them- 

 selves in morphogenetic pattern, which 

 among other activities sets the specific site 

 and amount of ossification in a given element. 

 (1) In the rat fetus the time of appearance 

 of bone salts and the specific locus of their 

 deposition varies from one skeletal element 

 to another (Bloom and Bloom, '40). (2) 

 Prospective ("undifferentiated") osteogenic 

 tissue of skeletal elements, such as the jaw 

 (Meckel's cartilage and membrane bone), 

 femur, and palatoquadrate bar, when iso- 

 lated from the chick embryo (SVo- to 6-day) 

 and grown separately as explants in vitro 

 shows a remarkable capacity for independent 

 development of shape and histology. Differ- 

 ences in physiological properties are likewise 

 expressed, since phosphatase activity is found 

 in those elements that in normal develop- 

 ment ossify (e.g., femur and palatoquadrate) 

 but not in those that fail to ossify (e.g.. 



Meckel's cartilage). Thus, in the absence of 

 both blood and nerve supply each element 

 develops in its own characteristic fashion 

 almost exactly as it does in its appropriate 

 position in the body of the embryo (Fell, 

 '31). 



From these considerations it is apparent 

 that the pattern of the skeleton is already 

 mapped out in the early embryo long before 

 the onset of ossification or even chondrifica- 

 tion. Each element has acquired its own 

 intrinsic growth pattern and special physi- 

 ological properties for selecting and utilizing 

 calcium and phosphate from the common 

 blood pool of the fetus. The quantity of up- 

 take would appear to vary from one indi- 

 vidual element to another in accordance with 

 the amount of osteogenic tissue (calcifiable 

 tissue) formed or capable of being formed. 

 Furthermore, as the number of skeletal ele- 

 ments with osteogenic tissue increases, the 

 quantity of uptake would be expected to in- 

 crease progressively until the osteogenic po- 

 tentialities have reached a peak in their 

 expression. 



Although the pattern of osteogenic potency 

 is set early in the development of a given 

 skeletal element, its full expression in normal 

 bone growth is apparently dependent upon 

 a multiplicity of interconnected conditions, 

 chief of which are (1) availability of ade- 

 quate concentrations of calcium and phos- 

 phate in the blood; (2) presence of the para- 

 thyroid hormone, which plays an important 

 role in the mobilization and metabolism of 

 calcium; (3) the presence of vitamin D, 

 which apparently facilitates the utilization 

 of calcium and phosphate in ossification; (4) 

 internal secretions of the pituitary (growth 

 hormone), thyroid, and sex glands, which, 

 in influencing the growth process in general, 

 tend as a rule to have a nonspecific regula- 

 tory effect on the growth of bone; and (5) 

 mechanical factors (i.e., tension of muscle 

 and ligaments, etc.) that influence the final 

 surface modelling of the bones dixring the 

 later stages of their development. (For an 

 excellent and comprehensive treatment of the 

 subject see Clark, '52.) 



In conclusion, it will be apparent from the 

 foregoing condensed account that the develop- 

 ment of parathyroid activity presents prob- 

 lems of an intricate and complex nature. 

 The onset of secretory activity cannot be 

 considered separately from other physiolog- 

 ical activities, since all activities are co- 

 ordinated in maintaining steady states within 

 the fetal body. Future progress in elucidating 

 the physiological role of the fetal parathy- 



