612 



Ontogeny of Endocrine Correlation 



of the embryonic body is relatively slow up 

 to the 80-mm. stage, from which time onward 

 to the mid-fetal period (ca. 160 mm.) it 

 becomes much greater; and (3) the period 

 from 100 to 150 mm. is one in which the 

 most active development of sinusoidal cir- 

 culation takes place. Each gland is trans- 

 formed from nearly a solid ball of parenchym- 

 atous cells into a body of anastomosing 

 cords with intervening sinusoids. At the 160 

 mm. stage, almost immediately after sinu- 

 soidal circulation is well established, a 

 marked increase in the number of paren- 

 chymatous cells and concomitant increase in 

 the size of the glands occur. Thereupon cell 

 types possibly representing different phases 

 in the secretory cycle of the chief cell first 

 appear. 



It becomes apparent from the lines of 

 evidence just given that, although the essen- 

 tial cellular elements are present from very 

 early stages onward in the morphogenesis 

 of the parathyroids, it is not until the mid- 

 fetal period that the glands present a struc- 

 tiu-al pattern indicative of endocrine activity. 

 Whether such a pattern, however, marks 

 the initial time of active production and 

 release of the parathyroid hormone remains 

 uncertain of decision. 



A more reliable index to the onset of 

 functional activity is the relation of struc- 

 tural pattern of the parathyroids and the 

 mobilization of calcium in the blood of the 

 fetus. According to current theory, which 

 is based upon a considerable body of experi- 

 mental evidence on postnatal mammals, the 

 principal regulator of the secretion of the 

 parathyroids is the calcium level in the 

 blood. Moreover, a homeostatic relationship 

 appears to exist between the levels of calcium 

 (and phosphate) in the blood and the se- 

 cretory activity of the glands. From the 

 standpoint of theory only a few studies have 

 a bearing on the problem of the relationship 

 of calcium concentration to parathyroid ac- 

 tivity in the fetus. In both human (Nicholas 

 et al., '34) and dog (Hoskins and Snyder, 

 '33) the fetal serum calcium level is 1 to 2 

 mg. per cent higher than that of the mother, 

 suggesting that the fetal glands may be 

 functioning independently of the mother in 

 regulating calcium level. In keeping with 

 this view are the observations on the rat 

 (Sinclair, '42) that the fetal glands at term, 

 although constituting no more than 5 per 

 cent of the total weight of the adult glands, 

 are twice as large in proportion to fetal body 

 weight as are those of the adult. Moreover, 

 the activity of the fetal glands as judged 



by weight changes is suppressed by high and 

 stimulated by low maternal serum calcium 

 levels (high serum phosphorus likewise has 

 a stimulating effect). 



Although the fetus is obviously solely de- 

 pendent upon the mother for its source of 

 calcium and phosphorus, the question arises 

 as to whether the parathyroid hormone can 

 cross the placenta in either direction. That 

 the hormone may not pass the placenta in 

 either direction under normal conditions is 

 indicated in the dog by injecting parathyroid 

 extract (Collip) separately into the mother 

 and fetus (Hoskins and Snyder, '33). When 

 injected into the fetus the serum calcium is 

 raised in fetal but not in maternal blood; 

 when injected into the mother the serum 

 calcium is raised in the maternal but only 

 to a limited extent in the fetal blood (tends 

 to parallel the elevation of serum calcium 

 produced in the mother). In the rat the fetal 

 parathyroids, although greatly hypertrophied 

 (weight may be doubled over that of normal 

 controls) in parathyroidectomized mothers, 

 have no ameliorative effect, since such 

 mothers develop tetany 2 to 4 days before 

 term (Bodansky and Duff, '41a; Sinclair, 

 '42). On the basis of these results it may be 

 inferred that in the normal animal the fetal 

 hormone (assiuning its presence in the cir- 

 culation) is not transmitted across the pla- 

 centa to the maternal circulation. However, 

 whether the maternal hormone is trans- 

 mitted to the fetus remains uncertain. As a 

 tentative hypothesis it is suggested that the 

 transmission of calcium itself rather than of 

 the maternal hormone can better account for 

 the changes in the fetus which result from 

 disturbances in calcium concentration in 

 the maternal blood. 



To a high degree the fetus appears to be 

 autonomous in regulating the calcium (and 

 phosphate) levels in its blood, tending to 

 maintain uniform levels even under adverse 

 conditions in the mother. For example, the 

 fetus can mobilize calcium through the pla- 

 centa and apparently maintain normal cal- 

 cium levels even when only very low 

 concentrations of calcium are available in 

 the maternal circulation. If, however, the 

 maternal calcium concentration falls below 

 a certain critical level, the fetal serum 

 calcium level becomes subnormal and there- 

 by calls forth compensatory activity, as is 

 reflected in the hypertrophy of the fetal para- 

 thyroids (Bodansky and Duff, '41b; Sinclair, 

 '42). As in the adult, regulation in the fetus 

 (at the latter stages of fetal life) seemingly 

 involves the integrated cooperation of a va- 



