CENTRAL CONTROL OF PITUITARY SECRETION 



1027 



might be obtained in the human by a careful and 

 well-controlled study of the potentiality of hypnotic 

 suggestion to modify endocrine activity, such as a 

 study of the concentration of protein-bound iodine 

 in the blood following the suggestion of a cold external 

 environment. 



At the present time data relating different cerebral 

 cortical areas, rhinencephalic structures or other 

 regions of the nervous system to anterior pituitary 

 function are scanty. The general implication in many 

 reports [see the excellent review by Kliiver (202)] is 

 that the hypothalamus and hypophysis form a basic 

 unit underlying endocrine activit)' but that other 

 areas of the central nervous system may exert a regu- 

 lating influence through projections to the hypothala- 

 mus. The term 'basic unit" is used since there is some 

 evidence that animals in which the hypothalamus has 

 been entirely separated from the rest of the central 

 nervous system may show signs of hypothalamo- 

 neurohypophysial function (i.e. normal water balance, 

 no polyuria) and of hypothalamoadenohypophysial 

 function (i.e. development of estrus) (15), although 

 such signs of function may be absent after hypotha- 

 lamic lesions or section of the pituitary stalk. Observa- 

 tion of the effects of lesions in distant parts of the 

 central nervous system on endocrine function were 

 made by Kliiver & Bartelmez (203) on a monkey 

 subjected to bilateral removal of both prefrontal 

 lobes and temporal lobes. This animal developed, 

 among other signs, polydipsia, bulimia with progres- 

 sive adiposity, hyperplasia of the rete o\arii and an 

 extensive endometriosis, results which the authors 

 felt might be attributed to degeneration of fibers to 

 the hypothalamus. Lesions in the region of the amyg- 

 daloid nuclei are now well known to result in abnor- 

 mal sexual behavior, but such a result may be due to 

 factors other than endocrine dysfunction. A more 

 direct relationship between the amygdaloid nuclei and 

 endocrine activity is that reported by Woods (362) 

 who found that lesions in the amygdaloid nuclei of 

 wild rats results in atrophic changes in the adrenal 

 glands. Richter (281) has noticed that similar lesions 

 in the wild rat tend to restore regular activity cycles 

 which are, in all probability, related to the estrous 

 cycles of these animals. Porter (271) has also drawn 

 attention to a possible relationship between the hippo- 

 campal region and the secretion of ACTH. He reports 

 that electrical stimulation of the hippocampal area, 

 in particular the uncus, in monkeys inhibited the 

 eosinopenia which normally follows administration 

 of epinephrine or operative trauma. In further experi- 

 ments the same worker found that electrical stimula- 



tion of the orbital surface of the frontal lobe resulted 

 in a marked eosinopenia. Such observations as those 

 just mentioned may safely be taken as the starting 

 point in a wide and new field of research. At the 

 moment the significance of such results is difficult to 

 interpret. In several cases the endocrine effects may 

 be secondary to changes in the 'emotional state' of the 

 animal, rather than due to a direct effect of the region 

 under investigation on the hypothalamus. However, 

 one may be sure that experimental data in this field 

 will be rapidly forthcoming in the future. 



ENDOCRINE ACTIVITY AND DEVELOPMENT OF NERVOUS 



SYSTEM. It has been suggested that, in a general way, 

 the pituitary stalk may be looked upon as the ana- 

 tomical and functional link between the endocrine 

 system and the external environment. In this case the 

 cjuestion may be asked at what stage in the develop- 

 ment of the organism does the stalk become function- 

 ally active, taking into consideration the fact that 

 exposure to a varying environment occurs only after 

 birth. Detailed discussions of this topic are available 



('55' I96)- 



The gonads, thyroid and adrenal corte.x appear to 

 be functionally active and secreting hormones before 

 birth. There is also evidence that the activity of the 

 fetal adrenal cortex is to some extent dependent on 

 the secretion of ACTH by the fetal pituitary For 

 example, removal of the pituitary (i.e. decapitation) 

 of the rat or rabbit fetus results in adrenocortical 

 atrophy (195, 348), although decapitation combined 

 with the injection of ACTH in the rat fetus increases 

 the size of the gland above the controls (348). There 

 is also evidence that a feed-back mechanism exists in 

 the fetal pituitary-adrenal cortex system, as in the 

 adult, since Kitchell & Wells (199) found that corti- 

 sone prevents compensatory hypertrophy of the 

 adrenal in the fetus. However, the well-known effect 

 of stress in discharging ACTH from the anterior 

 pituitary gland of the adult does not obtain in the 

 newborn. Jailer (191) found in rats that injection of 

 epinephrine does not excite pituitary discharge of 

 ACTH till the 8th day of life and that exposure to cold 

 was ineffective till the i6th day. Somewhat similar 

 results were obtained by Thompson & Blount (327) 

 in newborn mice. Now since the adrenal cortex of the 

 newborn animal is able to respond to injection of 

 ACTH (37, 192, 283, 327), and since Rinfret & Hane 

 (2B3) have shown the anterior pituitary of 4- to 

 7-day-old rats contains appreciable amounts of 

 ACTH, the possibility is raised that the lack of sensi- 

 tivity of the pituitary-adrenal axis of the newborn 



