Ontogeny of Endocrine Correlation 



585 



discovery of Courrier ('51) that radioactive 

 thyroxine, when injected intravenously into 

 normal male rabbits, is concentrated selec- 

 tively in the posterior pituitary. 



ANTERIOR PITUITARY-ADRENAL 

 RELATIONS 



Another functional relationship established 

 during the course of development of the em- 

 bryo is that between the anterior pituitary 

 and the adrenal glands. In the main the evi- 

 dence for this relationship is derived from a 

 study of the effects of (a) extirpation or de- 

 struction of the primordia of the anterior lobe 

 or of the adrenal gland and (b) grafting of 

 the anterior pituitary or administration of its 

 extracts from adult animals. 



ADRENOCORTICOTROPHIC EFFECTS ON 



DEVELOPMENT OF ADRENAL 



CORTEX 



That the development of the adrenal 

 glands is altered after removal of the in- 

 growing primordium of the anterior pituitary 

 in the anuran embryo was first demonstrated 

 by Smith ('20). The cortical or interrenal 

 tissue (in the form of profusely branched 

 cords of cells) is greatly diminished in 

 quantity as compared with that of the normal 

 or thyroidectomized tadpole of the same age 

 (in the thyroidectomized larvae the cortical 

 tissue is hypertrophied). The lipid granules 

 of the cortical cells show a change in re- 

 action to osmic acid, being less intensely 

 blackened as compared to the normal or to 

 the thyroidless tadpole. The diminution in 

 the cortical elements and alteration of the 

 lipid granules may be attributed to the ab- 

 sence of some essential trophic substance, 

 since injection of an extract of fresh bovine 

 anterior lobe into hypophysectomized tad- 

 poles restores the scanty adrenal cortex to 

 normal (Smith and Smith, '23). 



That the anterior pituitary exerts a trophic 

 action on the adrenal cortex of the mam- 

 malian fetus and the chick embryo is like- 

 wise clearly indicated. Destruction of the 

 hypophysis of the 13-day mouse fetus by 

 x-irradiation (Raynaud and Frilley, '50) or 

 decapitation of the rabbit fetus at 19 to 22 

 days (Jost, '48, '51a), of the rat fetus 2-4 

 days before term (Wells, '48) and of the 

 chick embryo at 40 to 50 hours (Case, '52), 

 usually leads to a marked diminution in 

 voliune of the adrenal cortex, and according 

 to Jost equally so in both sexes. Histologically 

 the cortex is atypical. The cortical cells are 



not only smaller and fewer in number as 

 compared with the normal bvit also show a 

 diminution in lipid granules and of ascorbic 

 acid as well in the chick. Similarly, a reduc- 

 tion in size of the adrenal cortex occurs in 

 the human fetus in cases of spontaneous 

 anencephaly and cyclopia, but only when the 

 anterior lobe is distinctly smaller than nor- 

 mal or completely absent (see Edmvmds, '50). 

 From the above observations it is clear that 

 the effects of removing the pituitary, irrespec- 

 tive of the means employed, lead to retro- 

 gressive changes in the adrenal cortex of the 

 embryo or fetus. These changes may be 

 attributed to the absence of a specific pitui- 

 tary hormone, since administration of adre- 

 nocorticotrophin (ACTH) to the hypophysec- 

 tomized embryo or fetus restores the adrenal 

 cortex more or less completely to its normal 

 volume and histology (Jost, '51a,b; Kitchell 

 and Wells, '52a; Case, '52). The results not 

 only indicate that the anterior pituitary of 

 the mammalian fetus and chick embryo at 

 least during the later stages of development 

 produces a hormone comparable in action to 

 ACTH, but also sviggest that this specific 

 hormone is essential for the normal histo- 

 genesis and growth of the cortical component 

 of the adrenal gland. 



EFFECTS OF ADRENAL CORTEX ON 

 ANTERIOR PITUITARY 



Does the adrenal cortex in turn have a 

 reciprocal action upon the anterior pituitary 

 of the developing embryo? According to 

 Tobin ('39) total or partial destruction of the 

 adrenal glands of the rat fetus (17 days and 

 older) by electric cautery results in cellular 

 changes in the pituitary. In comparison with 

 normal controls, the number of acidophiles 

 is decreased, the basophile cells show de- 

 granulation, and the number of chromophobe 

 cells appears to be increased. These results, 

 although suggestive of a reverse influence, 

 need confirmation and extension. That the 

 anterior pituitary is reactive to secretions of 

 the adrenal cortex during late fetal stages of 

 the rat is indicated by the recent investiga- 

 tions of Kitchell and Wells ('52b). After 

 unilateral adrenalectomy of the rat fetus on 

 the twentieth day, the intact adrenal under- 

 goes a compensatory hypertrophy that can be 

 prevented by subcutaneous implants of corti- 

 sone. Implants of cortisone to the normal 

 fetus of the same age fail to produce any 

 significant change in the volume of the 

 adrenal or the histology of the cortex. These 

 results seem to indicate that the liberation 



