IOI4 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOG\' U 



agent which has been found to prevent a stress 

 response on the part of the adrenal cortex is mor- 

 phine. [See the excellent review of their work by 

 Munson & Briggs (247) and the later confirmatory 

 work of Ohler & Sevy (253).] Morphine effectively 

 blockades the normal response to injection of hista- 

 mine, epinephrine, vasopressin, surgical trauma and 

 unilateral adrenalectomy. On the likely assumption 

 that morphine exerts its action at some point in the 

 central ner\ous system, possibly in the hypothalamus, 

 Munson & Briggs argue that these data make it seem 

 unlikely that histamine, epinephrine or vasopressin 

 play any essential part in the normal activation of 

 pituitary ACTH secretion. However it is also possible 

 that morphine acts in some way directly on the pitu- 

 itary gland. In that case the finding of Ohler & Sevy 

 (253) may be of more physiological significance — that 

 injection of adrenal cortical extract blocks the ACTH 

 response to operative stress and to administration of 

 sympathomimetic amines but, even in large doses, 

 has little effect against vasopressin-induced adrenal 

 ascorbic acid depletion. 



In the last few years data have been brought for- 

 ward relating the hormones of the neurohypophysis 

 to humoral activation of the adcnohypophysis. If this 

 is substantiated an obvious correlation would be ap- 

 parent, from the teleological viewpoint, Ijetween the 

 embryological formation of the adcnohypophysis and 

 its mode of regulation. The evidence may be sum- 

 marized as follows. 



(i) In vitro studies. Pars distalis tissue has been 

 cultured in roller tubes by Guillemin and his co- 

 workers (137, 139-141). They found that .such cul- 

 tures did not release ACTH into the fluid medium 

 after the 8th day of incubation unless explants of the 

 hypothalamus or median eminence were added to the 

 culture. Control tissue in the form of cerebral cortex, 

 liver or spleen was without effect. Data were produced 

 that histamine, acetylcholine, 5-hydroxytryptamine 

 (serotonin), oxytocin, norepinephrine and vasopressin 

 (all known to be present in the hypotlialamus) were 

 not the compounds responsible for the effect of 

 hypothalamic tissue (141). However commercial 

 pitres.sin was active in this respect, although purified 

 arginine-vasopressin was not; therefore the conclusion 

 was drawn that the effect of the commercial extract 

 was due to some fraction extracted with the posterior 

 pituitary hormone (139). Results obtained after frac- 

 tionation of hypothalamic and crude posterior pitui- 

 tary extract are in agreement with this view (140). 

 The independent studies of Saffran and his colleagues 

 in Montreal (290-292) are in general agreement. 



These workers used incubated pituitary and adrenal 

 tissue in a more acute type of experiment and a 

 chemical method for measuring the adrenal corticoids 

 released into the incubation medium. An ACTH- 

 releasing factor was found in posterior pituitary ex- 

 tracts and in vasopressin prepared by the method of 

 Stehle and Fraser. Howe\er the ACTH-releasing 

 factor was found to be distinct from vasopressin and 

 o.xvtocin, and its activity was found to be enhanced 

 by norepinephrine. The active substance has now 

 been isolated by paper chromatography. 



h) In vivo studies. McCann & Brobeck (234) have 

 reported that injection of large doses of vasopressin 

 increases adrenocortical activity in the rat. Sayers & 

 Burks (300) and Sayers (299) find that pitressin, 

 extracts of the rat neurohypophysis and du Vigneaud's 

 purified vasopressin increa.se the blood level of ACTH 

 in the adrenalectomized and anesthetized rat. Pitocin, 

 epinephrine and extracts of spleen, muscle or liver 

 were inacti\e in this respect. Some experiments on 

 the human (239, 314) have shown that administra- 

 tion of pitressin is more effective in evokine; adreno- 

 cortical activity than pitocin. Studies of hypothalamic 

 lesions have shown a relationship between the site of 

 lesions which produce diabetes insipidus and those 

 which block .'^CTH discharge in response to stress 

 (234), and those that prex'ent compensatory hyper- 

 trophy of the adrenal cortex which normally follows 

 unilateral adrenalectomy (113). Martini and his 

 colleagues (227-229) have found that antidiuretic 

 and oxytocic hormones cause signs of adrenal activa- 

 tion when injected into normal, but not hypophy- 

 sectomized, rats. They obtained evidence that this 

 was a direct effect on pars distalis tissue by experi- 

 ments utilizing intraocular anterior pituitary trans- 

 plants. 



The possibility that the release of lactogenic hor- 

 mone from the pars distalis is stimulated by oxytocic 

 hormone has been raised by the observations of 

 Benson & Folley (25). They found that the mammary 

 glands of lactating female rats from which the litters 

 liad been removed were maintained in a more active 

 state if repeated injections of oxytocin were given. 



A relationship between TSH secretion and pos- 

 terior pituitary hormone has also been suggested. 

 Dubreuil & Martini (86) have reported that the up- 

 take of radioactive iodine by the thyroid gland of 

 male rats is increased by previous administration of 

 vasopressin, and Harris & Woods (164, 165; un- 

 published observations) find that electrical stimula- 

 tion of the hypothalamus in the region of the supra- 

 opticoh\ pophysial tract, known to be effective in 



