586 



of ACTH, which appears to be essential for 

 compensatory hypertrophy of the adrenal, is 

 suppressed by the administered cortisone. 



INTERRELATIONS IN TIME OF ONSET 

 OF FUNCTIONAL ACTIVITY 



As to the time of onset of functional activ- 

 ity in the anterior pituitary and adrenal 

 cortex during the course of their develop- 

 ment no precise information is available. 

 However, certain inferences may be drawn 

 from the data at hand (see Table 27). The 

 preceding analysis indicates that the primor- 

 divun of the adrenal gland is responsive to 

 ACTH in the rat and mouse during the last 

 third and in the rabbit during the last 

 fourth of the period of gestation. Apparently 

 the period before term is one in which the 

 constituent cortical and medullary cells are 

 assuming step by step an orderly arrange- 

 ment or oriented cell pattern simvilating that 

 characteristic of the adult gland. It is a 

 period of active morphogenesis and to some 

 extent histogenesis. Using the movise fetus as 

 an example, it is seen according to Waring 

 ('35) that on about the thirteenth day the 

 cortical and medullary primordia are both 

 constituted and closely adpressed. By the 

 fourteenth day the sympathochromaffin ele- 

 ments have begun to migrate into the 

 cortical component, the immigration con- 

 tinuing gradually until the day of birth, 

 when they are concentrated at the center of 

 the gland. The cells of the cortex at 14 days 

 are all more or less alike (finely granular 

 and highly eosinophilic cytoplasm), and 

 their arrangement is haphazard. Between the 

 sixteenth day and term an oriented pattern 

 of cortical cells arises. The cells at the periph- 

 ery of the cortex become less eosinophilic 

 between the sixteenth and eighteenth days, 

 and at birth have an arrangement which 

 merely foreshadows that characteristic of the 

 glomerular and fasciculate zones of the per- 

 manent cortex. Internal to this apparent fore- 

 runner of the permanent cortex and inter- 

 locking with the medullary cells is a zone 

 of more highly eosinophilic cortical cells, the 

 beginning of the so-called "fetal cortex," 

 "x-zone" of Miller, or "androgenic zone." 



It may be inferred, therefore, that at the 

 time of experimental removal of the pitui- 

 tary in the mammalian fetus the adrenal 

 cortex is clearly responsive to adrenocortico- 

 trophic hormone after the cortical and med- 

 ullary primordia ai-e already constituted and 

 combined, and especially so during the sub- 

 sequent critical stages of morphogenesis and 



Ontogeny of Endocrine Correlation 



histogenesis of the two component tissues. 

 The nature of the effect appears to be that of 

 retarded or arrested morphogenesis, rather 

 than degeneration. No evidence is available 

 as to whether the adrenal at still earlier 

 stages can respond to ACTH. This problem 

 might be resolved by growing the primordia 

 of anterior pituitary and adrenal in juxta- 

 position, either by grafting or by in vitro cul- 

 tures, since activation by local diffusion of 

 hormones appears to be a more sensitive test 

 than activation by hormones that pass 

 through the regular blood vessels of the 

 embryo (see p. 583). Also, since ACTH 

 definitely stimulates adrenocortical growth 

 in the rat as early as the fourth day after 

 birth (Moon, '40), the time and degree to 

 which adrenocortical growth is stimulated 

 might be ascertained by injection of ACTH 

 into fetuses at successively earlier stages. 



Whether the growth of the primordia of 

 the permanent cortex or the "fetal cortex" is 

 equally or differentially affected by the ab- 

 sence of anterior pituitary is a problem of 

 much significance. An inhibition of the 

 growth of the permanent cortex is to be ex- 

 pected, since in the dwarf mouse, which has 

 an endocrine-deficient anterior pituitary, the 

 characteristic zoning of the cortex is absent 

 or indistinct (Smith and McDowell, '30). 

 Possible effects on the growth of the fetal 

 cortex are of special interest in many mam- 

 mals (such as mouse, rabbit, cat, human, 

 certain carnivores and ungulates), since it 

 is proportionally very large, constituting the 

 main bulk of the cortex. In some species its 

 growth is relatively enormovis, taking place 

 during either fetal or early postnatal life. 

 This hypertrophy apparently is responsible 

 for the relatively large size of the adrenal 

 gland at birth (Hill, '30). In man at birth, 

 for instance, the adrenals constitute 0.2 per 

 cent of the entire body weight, contrasting 

 with 0.1 per cent for the adult (Scammon, 

 '30). The only clues that pituitary secretions 

 possibly regulate the growth of the fetal 

 component have been reported by Elliot and 

 Armour ('11), who attributed the small size 

 of the adrenal of an anencephalous human 

 infant (at birth) to an almost complete ab- 

 sence of the fetal cortex, and by Deanesley 

 ('38), who demonstrated that in pituitary- 

 deficient dwarf mice the x-zone is absent in 

 spite of normal reproductive activity. More- 

 over, in early postnatal life the fetal cortex 

 often shows a distinct sex difference, per- 

 sisting longer and attaining a larger size in 

 females than in males. Although often re- 

 garded as having possible androgenic fvmc- 



