Ontogeny of Endocrine Correlation 



589 



in ascorbic acid content during the period 

 under consideration apparently constitute a 

 reliable indicator of functional activity, since 

 in pituitaryless embryos the quantity of as- 

 corbic acid does not rise but remains at a 

 level characteristic of the adrenals of the 

 normal 12-day embryo. Treatment of such 

 pituitaryless embryos with ACTH brings 

 about an apparent increase in sudanophilic 

 lipids of cortical tissue, but whether ascorbic 

 acid is likewise increased has not been de- 

 termined. 



The lack of information on the possible 

 occurrence of ascorbic acid in the adrenal 

 of the mammalian fetus is a challenge. In 

 juvenile and adult mammals the concentra- 

 tion of ascorbic acid (as well as of choles- 

 terol) is regulated by the anterior pituitary. 

 The administration of ACTH and stress 

 (several varieties) both bring about a marked 

 reduction or depletion of ascorbic acid (for 

 a recent consideration and references see 

 Sayers and Sayers, '49, and Long, '49). In 

 all probability ascorbic acid accumulates 

 along with sudanophilic lipids which, as 

 noted above, occur in the developing adrenal 

 cortex. Microchemical and histochemical 

 tests for the presence of ascorbic acid, es- 

 pecially if correlated with alterations in its 

 content imder conditions of increased acti- 

 vation, should prove to be valuable methods 

 for the evaluation of the degree of cortical 

 activity, if any, in the fetus or during early 

 postnatal life. Progressive changes in the 

 mechanism of response are indicated in in- 

 fant rats of increasing age. According to 

 Jailer ('50) the ascorbic acid content of the 

 adrenal declines (24 to 37 per cent) in re- 

 sponse to the administration of ACTH to 

 animals 4 to 6 days of age, but no decline 

 occurs upon exposure of the animals to a 

 temperature of 5°C. (stress) until the six- 

 teenth day; also, the administration of adren- 

 aline (epinephrine) causes no increase in 

 ascorbic acid until the eighth day. Further, 

 using fall in ascorbic acid content as an 

 index of activation, no ACTH activity in 

 the anterior pituitary of infant rats is de- 

 tectable until the eighteenth day of age post 

 partum (Jailer, '51). 



Such combined methods of attack now 

 seem feasible for determining cortical activ- 

 ity in the fetus, since at least for a short 

 period prior to birth the adrenal cortex is re- 

 sponsive to adrenocorticotrophic hormone as 

 noted above. In a similar way the changes in 

 birefringent substances may furnish addi- 

 tional clues (Yoffey and Baxter, '47). Special 

 attention shovdd be directed to the histo- 



chemical detection of cholesterol esters, cor- 

 tical sterones, and ascorbic acid, substances 

 known to be present in the functionally ac- 

 tive cortex of the adult mammalian adrenal 

 (Yoffey and Baxter, '49). Whether the cortex 

 of the mammalian embryo at any stage con- 

 tains these substances or chemically related 

 ones has not yet been established. Tests for 

 the occurrence of these substances would 

 have a twofold purpose: (1) to ascertain the 

 period when the growing cortex acquires the 

 capacity to select steroid mother substances 

 from the blood and synthesize them into 

 cortical sterones or allied compounds, and 

 (2) to determine whether such capacity is 

 a key to the approximate time when adreno- 

 corticotrophic substance is released by the 

 anterior lobe in quantities sufficient for cor- 

 tical activation. Progress along these lines 

 has been made by Dawson ('53) in a study 

 of the time course in histochemical differ- 

 entiation of the adrenal gland of the chick 

 embryo. As judged by their reactions to given 

 chemical agents or by birefringent proper- 

 ties, several kinds of lipid compounds appear 

 in some cords of the gland as early as the 

 seventh day but are not common to all cords 

 until the eleventh or twelfth day; on the 

 basis of the silver reaction, ascorbic acid, 

 although first detectable on about the tenth 

 day, is not present in appreciable quantities 

 until the twelfth day. 



Turning next to the functional activity of 

 the anterior pituitary, very little is known 

 concerning the time when adrenocorticotro- 

 phic substance begins to form, the rate of its 

 increase, or whether its production is cor- 

 related with the differentiation of cell types 

 (see Table 27). That the anterior pituitary 

 is active in producing and releasing ACTH 

 during the last third or quarter of fetal 

 life in the rat and rabbit and of the last 

 third of the embryonic period of the chick 

 is clearly indicated, since within that period 

 the growth of the adrenal cortex is definitely 

 arrested in the absence of the pituitary and 

 can be restored to normal or partially so 

 by administration of adrenocorticotrophin. 

 Apparently, then, for a short period prior to 

 birth or hatching the trophic hormone in 

 question is present in sufficient concentration 

 to be physiologically effective. This may 

 mark the peak production during embryonic 

 life of the species under consideration. 



It is of interest to note parenthetically that at 

 about this time signs of thyroid activity are first 

 noted in the rat fetus. In this species the thyroid 

 does not begin to form follicles and store colloid 

 until 3 to 4 days prior to birth, becoming more 



