590 



Ontogeny of Endocrine Correlation 



marked immediately before term (Kull, '26). It is 

 within this period, i.e., at 18 to 19 days of gestation, 

 that the thyroid first acquires the capacity to con- 

 centrate radioactive iodine; the capacity is consid- 

 erably stronger at birth (Gorbman and Evans, '43). 

 Also, between the I9I/2 day and term, the thyroid of 

 normal and pituitaryless rat fetuses is reactive to 

 subcutaneous injections of thyrotrophin (Sethre 

 and Wells, '51). From the presumptive evidence at 

 hand, it would appear that in the rat fetus the endo- 

 crine functions of the thyroid, anterior lobe, and 

 adrenal cortex begin relatively late, i.e., at a time 

 when nearly 90 per cent of the intra-uterine life is 

 completed. 



Whether the anterior pituitary at early 

 stages has ACTH activity is not known but 

 might be tested in the manner suggested on 

 pp. 582 and 583. Likewise, no information is 

 available on whether the production of 

 ACTH increases quantitatively with develop- 

 mental age. It probably increases rapidly 

 after birth, judging from the marked changes 

 that take place in the growth and vascularity 

 of the adrenal cortex in the rat, mouse, and 

 man. 



No systematic attempt has been made to 

 correlate the onset of adrenocorticotrophic 

 activity with the time course of differen- 

 tiation of the cell types in the anterior 

 pituitary. Of those species in which trophic 

 activity is indicated, only in the anuran, 

 chick, and rat embryos has the occurrence 

 of cell types been reported. In the anuran 

 no relationship is ascertainable since the 

 anterior lobe is removed at a very early stage, 

 long before the histogenesis of cell types 

 begins. Although in the rat, acidophiles, 

 basophiles, and chi'omophobe cells are al- 

 ready differentiated in fetuses of 18 to 23 

 days (Tobin, '39), the time order of their 

 differentiation and numerical frequency 

 have not been investigated. In the chick a 

 close correspondence is seen between the 

 indicated period of adrenocorticotrophic ac- 

 tivity and active histogenesis of the cell 

 types. Subsequent to the tenth day, when 

 they are first apparent, the acidophiles rap- 

 idly increase in number, becoming the pre- 

 dominating type of cell by the eighteenth 

 day (Rahn, '39) or at most by the third day 

 after hatching (Payne, '46). Althovigh baso- 

 phile-like cells seem to be present from the 

 twelfth day on, typical basophiles are not 

 found until after hatching (cf. Wilson, '52). 



That the cellular source of the hormone 

 in the embryonic development of the pitui- 

 tary is by no means clear is not surprising, 

 since even in postnatal mammals at variovis 

 ages it has been difficult to assign a specific 

 hormonal secretion to any particular cell 



type. Reports as to the cellular source of 

 ACTH are diverse and often contradictory, 

 as the following selected examples show. 

 Presumptive evidence that at least one cell 

 type plays a role in the secretion of adreno- 

 corticotrophin is found in the hereditary 

 dwarf mouse (homozygous for a recessive 

 dwarfing gene), in which adrenal cortical 

 aplasia is associated with the complete ab- 

 sence of typical acidophiles in the anterior 

 pituitary (Smith and McDowell, '30). Al- 

 though these authors were uncertain as to 

 the identification of the other cell types, 

 later studies by Francis ('44) on the fully 

 grown dwarf show that the basophiles are 

 likewise absent and the number of typical 

 chromophobes is markedly reduced (small 

 pyknotic acidophiles and chromophobes com- 

 prise the predominating types of cell). More 

 recently, Finerty and Briseno-Castrejon ('49) 

 suggested that the acidophiles secrete ACTH 

 since a marked increase in the percentage of 

 these cells occurs in the anterior pituitary, 

 following unilateral adrenalectomy in the 

 immature male rat. Still more recently, Mar- 

 shall ('51) was able to show by means of a 

 fluorescent antibody technique adapted to 

 the localization of antigens in cells and 

 tissues that a solution of fluorescent antibody 

 (to pig ACTH) stains selectively the cyto- 

 plasm of basophile cells of the pig pituitary. 

 The reaction is highly specific, since cells of 

 the sheep or bovine pituitary do not stain. 



In any investigation of the problem of the 

 cellular source of the hormone in pituitary 

 development special attention should be 

 given to the time order of differentiation of 

 the cell types as well as to their progressive 

 changes in numerical frequency and in cyto- 

 logical characteristics. Such an approach, 

 when combined with experimental pro- 

 cedures designed to bring about an imbal- 

 ance in the normal functional interaction of 

 the adrenal cortex (and other receptor 

 glands) and anterior pituitary, should prove 

 of value in elucidating the problem. For 

 the specific localization of ACTH in cells 

 during the histogenesis of the anterior pi- 

 tuitary the fluorescent antibody technique is 

 undoubtedly the most promising of all. 



ON THE ROLE OF ADRENALINE AS A 



CORRELATING HORMONE IN 



THE PITUITARY-ADRENAL 



SYSTEM 



As may be seen from an inspection of 

 Table 27, the substance adrenaline* arises 



* According to Shepherd and West ("51). in fetal 

 (near term) and early postnatal stages of various 



