588 



Ontogeny of Endocrine Correlation 



arrangement of the capillaries is first noted 

 in the pig fetus (12 to 15 cm.) at a stage 

 when the definitive topographical relations 

 of cortex and medulla are first established. 

 During subsequent stages the capillary 

 plexus assumes gradually a more orderly 

 arrangement, and at a stage just before birth 

 (22 cm. fetus) it has a distinct longitudinal 

 orientation, although still of a much simpler 

 pattern than in the adult (see Fig. 209C). 



Species variations in the time of origin of 

 an oriented pattern of circulation are ex- 

 pected. In the mouse, for example, the per- 

 manent cortex is much less well organized 

 than it is in the pig at birth. Subsequent 

 to birth in the mouse the cortical cells (pe- 

 ripheral to x-zone) gradually assume the form 

 of parallel cords in the fasciculate zone, only 

 becoming distinct at about 25 days after 

 birth. On the assumption that column for- 

 mation and orientation of circulation are 

 causally related, the capillary plexus should 

 gradually change to a longitudinal orienta- 

 tion. By the fourth week, at any rate, the 

 pattern of circulation is clearly an oriented 

 one (Gersh and Grollman, '41). 



A further criterion of beginning functional 

 activity is the time of appearance, rate of 

 accumulation, and identification of the kinds 

 of lipids of the cortex during development. 

 It has commonly been inferred that the 

 lipids of the cortical cells may be the ve- 

 hicle for cortical hormones, since they are 

 obtained primarily from the lipid fraction of 

 extracts of adult adrenal glands. In the hu- 

 man embryo lipids in the form of fine drop- 

 lets are already present in the cortical cells 

 at the stage (14 mm.) of initial penetration 

 of the future medullary cells into the cortical 

 primordium. Generally speaking, during sub- 

 sequent stages in adrenal development the 

 amount of sudanophilic lipids seems to in- 

 crease in the permanent cortex and to dimin- 

 ish in the fetal cortex. In the latter the lipids 

 gradually diminish during the later weeks 

 of intra-uterine life, disappearing altogether 

 at full term (in the postnatal mouse the 

 homologous x-zone prior to onset of its de- 

 generation is likewise free of sudanophilic 

 lipids according to Howard-Miller, '27). Con- 

 comitantly with the active growth and or- 

 ganization of the layers of the permanent 

 cortex the amount of lipid increases. An 

 increase in lipids over earlier stages is in- 

 dicated at birth when the cortical cells 

 show a beginning arrangement into colimins, 

 a further increase at 3 weeks after birth 

 when the fascicular zone is better defined, 

 and a well-marked increase in the glomer- 



ular and fascicular zones of a 3-month-old 

 infant (see Keene and Hewer, '27; Uotila, 

 '40). 



Although highly suggestive, this increase 

 in sudanophilic lipid, which apparently at- 

 tains its highest concentration at about the 

 time the permanent cortex acquires a well- 

 defined zonal organization, cannot be re- 

 garded by itself as a reliable indicator of 

 cortical hormone production. Sudan III does 

 not discriminate among the various kinds of 

 lipids. Neither does osmic acid, another com- 

 monly used reagent for detecting lipid sub- 

 stances in tissues. Nevertheless such histo- 

 chemical tests, although not useful alone 

 for a differential discrimination of lipids, 

 may be valuable indicators when applied to 

 the adrenal in which changes in cortical 

 activity have been induced experimentally. 

 For example, in the postnatal rat a definite 

 correlation exists between cortical activity 

 and reduction of osmic acid. The reduction of 

 osmic acid is increased by stimulation (in- 

 duced by unilateral adrenalectomy, cold, 

 etc.) and decreased by depression (induced 

 by injection of variable amounts of cortical 

 hormone) of cortical activity (Flexner and 

 Grollman, '39). Furthermore, the same type 

 of dynamic change in sudanophilic lipids 

 (possibly cholesterol esters) occurs in the 

 adrenal cortex of rats following administra- 

 tion of ACTH or subjection to stress. These 

 changes parallel the alterations in cholesterol 

 content (Sayers et al., '44). 



Still another possible key to the onset of 

 adrenal cortical activity in the fetus is the 

 time and rate of accumulation of the vita- 

 min, ascorbic acid, which along with choles- 

 terol esters occurs in high concentration in 

 the functionally active adrenal of juvenile 

 and adult mammals. Only a few attempts 

 have been made to determine the presence 

 of ascorbic acid in the developing adrenal of 

 any vertebrate. By means of a colorimetric 

 method Case ('52) found that the quantity 

 of ascorbic acid rapidly increases in the 

 chick adrenals from the twelfth to the 

 nineteenth day of incubation, rising from a 

 value of 0.95 to 1.67Mg. per milligram of 

 adrenal tissue during this period. The further 

 observation that the total amount of ascorbic 

 acid increases relatively more rapidly than 

 does the net weight suggests that with ad- 

 vancing age the adrenals acquire an increas- 

 ing capacity to accumulate ascorbic acid. 

 Unfortunately the initial time and rate of 

 accumulation have not yet been determined 

 for adrenals of embryos earlier than the 

 twelfth day (cf. Dawson, '53). The changes 



